Sample records for carbogen inhalation increases

  1. Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease Increased oxygen transport to hypoperfused brain

    DEFF Research Database (Denmark)

    Ashkanian, Mahmoud; Gjedde, Albert; Mouridsen, Kim


    comparisons by an additive ANOVA model showed that carbogen significantly increased CBF by 7.51 + or - 1.62 ml/100 g/min while oxygen tended to reduce it by -3.22 + or - 1.62 ml/100 g/min. A separate analysis of the hemisphere contralateral to the hypoperfused hemisphere showed that carbogen significantly...... and Sa(O2) are readily obtained with carbogen, while oxygen increases only Sa(O2). Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone. Further studies with more subjects are, however, needed to investigate the applicability of carbogen for long-term inhalation...

  2. Temporal variation in the response of tumors to hyperoxia with breathing carbogen and oxygen

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    Hua-gang Hou


    Full Text Available The effect of hyperoxygenation with carbogen (95% O 2 + 5% CO 2 and 100% oxygen inhalation on partial pressure of oxygen (pO 2 of radiation-induced fibrosarcoma (RIF-1 tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and aggregates of oximetry probe, lithium phthalocyanine (LiPc, was implanted in each tumor. A baseline tumor pO 2 was measured by electron paramagnetic resonance (EPR oximetry for 20 minutes in anesthetized mice breathing 30% O 2 and then the gas was switched to carbogen or 100 % oxygen for 60 minutes. These experiments were repeated for 10 days. RIF-1 tumors were hypoxic with a baseline tissue pO 2 of 6.2-8.3 mmHg in mice breathing 30% O 2 . Carbogen and 100% oxygen significantly increased tumor pO 2 on days 1 to 5, with a maximal increase at approximately 32-45 minutes on each day. However, the extent of increase in pO 2 from the baseline declined significantly on day 5 and day 10. The results provide quantitative information on the effect of hyperoxic gas inhalation on tumor pO 2 over the course of 10 days. EPR oximetry can be effectively used to repeatedly monitor tumor pO 2 and test hyperoxic methods for potential clinical applications.

  3. Response of Hepatoma 9618a and Normal Liver to Host Carbogen and Carbon Monoxide Breathing

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    Simon P. Robinson


    Full Text Available The effects of hyperoxia (induced by host carbogen 95% oxygen/5% carbon dioxide breathing. and hypoxia (induced by host carbon monoxide CO at 660 ppm. breathing were compared by using noninvasive magnetic resonance (MR methods to gain simultaneous information on blood flow/oxygenation and the bioenergetic status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a 1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent (BOLD MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb, which acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin in the case of carbogen breathing, or carboxyhemoglobin with CO breathing. The results were confirmed by observation of similar changes in deoxyHb in arterial blood samples examined ex vivo after carbogen or CO breathing. There was no change in nucleoside triphosphates (NTP/PI in either tumor or liver after CO breathing, whereas NTP/Pl increased twofold in the hepatoma (but not in the liver after carbogen breathing. No changes in tumor intracellular pH were seen after either treatment, whereas extracellular pH became more alkaline after CO breathing and more acid after carbogen breathing, respectively. This tumor type and the liver are unaffected by CO breathing at 660 ppm, which implies an adequate oxygen supply.

  4. Inhalants (United States)

    ... which open the breathing passages. Inhalers are very safe when used as prescribed by doctors. Inhalants, on the other hand, are common household chemicals that contain a volatile component which can be ...

  5. Formation Mechanism of Carbogenic Nanoparticles with Dual Photoluminescence Emission

    KAUST Repository

    Krysmann, Marta J.


    We present a systematic investigation of the formation mechanism of carbogenic nanoparticles (CNPs), otherwise referred to as C-dots, by following the pyrolysis of citric acid (CA)-ethanolamine (EA) precursor at different temperatures. Pyrolysis at 180 °C leads to a CNP molecular precursor with a strongly intense photoluminescence (PL) spectrum and high quantum yield formed by dehydration of CA-EA. At higher temperatures (230 °C) a carbogenic core starts forming and the PL is due to the presence of both molecular fluorophores and the carbogenic core. CNPs that exhibit mostly or exclusively PL arising from carbogenic cores are obtained at even higher temperatures (300 and 400 °C, respectively). Since the molecular fluorophores predominate at low pyrolysis temperatures while the carbogenic core starts forming at higher temperatures, the PL behavior of CNPs strongly depends on the conditions used for their synthesis. © 2011 American Chemical Society.

  6. Deep inspiration increases the absorption of inhaled sodium cromoglycate. (United States)

    Richards, R; Fowler, C; Simpson, S F; Renwick, A G; Holgate, S T


    The plasma concentrations of sodium cromoglycate were measured for 4 h following a single dose of 20 mg given by inhalation to six normal volunteers. A series of forced expiratory manoeuvres was performed 2 h after the dose, which resulted in a rapid and marked increase in the plasma concentrations of the drug. A similar increase was found in three volunteers who undertook a single deep inspiration at 4 h. These data indicate that the absorption of cromoglycate from the airways can be affected by manoeuvres used to assess lung function. PMID:2503020

  7. Addition of a hypoxic cell selective cytotoxic agent (mitomycin C or porfiromycin) to Fluosol-DA/carbogen/radiation

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    Holden, S.A.; Teicher, B.A. (Dana-Farber Cancer Institute, Boston (USA)); Herman, T.S. (Dana-Farber Cancer Institute, Boston (USA) Joint Center for Radiation Therapy, Boston (USA))


    In an effort to develop effictive combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiaiton, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cytotoxicity of radiation (10 Gy) more in the bright cell subpopulation (4-fold) than in the dim cell subpopulation (2-fold) resulting in an overall 4-fold sparing of the dim subpopulation. Mitomycin C and porfiromycin were both more toxic toward the dim cell subpopulations. Addition of mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation (10 Gy) resulted in a primarily additive effect of the drugs and radiation killing in both tumor cell subpopulations. Thus, with mitomycin C/Fluosol-DA/carbogen and radiation there was a 2-fold sparing of dim cells and with profiromycin in the combined treatment a 1.6-fold sparing of the dim cell population. (Abstract Truncated)

  8. Lung deposition of inhaled drugs increases with age

    DEFF Research Database (Denmark)

    Onhøj, J; Thorsson, L; Bisgaard, H


    versus time (AUC). Terminal half-life (T(1/2)) was evaluated. Dose to patient, AUC, and T(1/2) were similar in the three age groups (p > 0.35). Nebuchamber delivers the same dose of budesonide to young children and adults. Yet the plasma concentration of budesonide was similar in young children...... and adults. Therefore, lung dose is increased with age. This suggests that from a safety perspective, the prescribed dose of budesonide inhaled from a pMDI with Nebuchamber spacer need not be adjusted for age or use of facemask. Children and adults can use the same nominal dose of budesonide via Nebuchamber...

  9. Photoluminescent carbogenic nanoparticles directly derived from crude biomass

    KAUST Repository

    Krysmann, Marta J.


    We present an environmentally benign, energy efficient and readily scalable approach to synthesize photoluminescent carbogenic nanoparticles directly from soft tissue biomass. Our approach relies on the pyrolytic decomposition of grass that gives rise to the formation of well-defined nanoparticles. The carbogenic nanoparticles can be readily surface modified, generating a series of highly selective photoluminescent materials that exhibit remarkable stability upon prolonged exposure to aggressive, high-temperature, high-salinity environment. © 2012 The Royal Society of Chemistry.

  10. Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

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    Chiyohiko Shindoh


    Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

  11. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction. (United States)

    Xu, Jiajun; Yang, Ming; Kosterin, Paul; Salzberg, Brian M; Milovanova, Tatyana N; Bhopale, Veena M; Thom, Stephen R


    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries.

  12. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

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    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)


    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  13. Evaluation and Immunohistochemical Qualification of Carbogen-Induced ΔR{sub 2}* as a Noninvasive Imaging Biomarker of Improved Tumor Oxygenation

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    Baker, Lauren C.J., E-mail: [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Boult, Jessica K.R.; Jamin, Yann; Gilmour, Lesley D.; Walker-Samuel, Simon; Burrell, Jake S. [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom); Ashcroft, Margaret [Division of Medicine, Centre for Cell Signalling and Molecular Genetics, University College London, London (United Kingdom); Howe, Franklyn A. [St. George' s, University of London, London (United Kingdom); Griffiths, John R. [Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Raleigh, James A. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); Kogel, Albert J. van der [University of Nijmegen Medical Centre, Nijmegen (Netherlands); Robinson, Simon P. [Cancer Research UK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)


    Purpose: To evaluate and histologically qualify carbogen-induced ΔR{sub 2}* as a noninvasive magnetic resonance imaging biomarker of improved tumor oxygenation using a double 2-nitroimidazole hypoxia marker approach. Methods and Materials: Multigradient echo images were acquired from mice bearing GH3 prolactinomas, preadministered with the hypoxia marker CCI-103F, to quantify tumor R{sub 2}* during air breathing. With the mouse remaining positioned within the magnet bore, the gas supply was switched to carbogen (95% O{sub 2}, 5% CO{sub 2}), during which a second hypoxia marker, pimonidazole, was administered via an intraperitoneal line, and an additional set of identical multigradient echo images acquired to quantify any changes in tumor R{sub 2}*. Hypoxic fraction was quantified histologically using immunofluorescence detection of CCI-103F and pimonidazole adduct formation from the same whole tumor section. Carbogen-induced changes in tumor pO{sub 2} were further validated using the Oxylite fiberoptic probe. Results: Carbogen challenge significantly reduced mean tumor R{sub 2}* from 116 ± 13 s{sup −1} to 97 ± 9 s{sup −1} (P<.05). This was associated with a significantly lower pimonidazole adduct area (2.3 ± 1%), compared with CCI-103F (6.3 ± 2%) (P<.05). A significant correlation was observed between ΔR{sub 2}* and Δhypoxic fraction (r=0.55, P<.01). Mean tumor pO{sub 2} during carbogen breathing significantly increased from 6.3 ± 2.2 mm Hg to 36.0 ± 7.5 mm Hg (P<.01). Conclusions: The combined use of intrinsic susceptibility magnetic resonance imaging with a double hypoxia marker approach corroborates carbogen-induced ΔR{sub 2}* as a noninvasive imaging biomarker of increased tumor oxygenation.

  14. Fractionated irradiation combined with carbogen breathing and nicotinamide of two human glioblastomas grafted in nude mice


    Sun, Lin-Quan; Buchegger, Franz; Coucke, Philippe; MIRIMANOFF


    This study addressed the potential radiosensitizing effect of nicotinamide and/or carbogen on human glioblastoma xenografts in nude mice. U-87MG and LN-Z308 tumors were irradiated with either 20 fractions over 12 days or 5 fractions over 5 days in air-breathing mice, mice injected with nicotinamide, mice breathing carbogen, or mice receiving nicotinamide plus carbogen. The responses to treatment were assessed using local control and moist desquamation. In U-87MG tumors, the enhancement ratios...

  15. Early Effects of Combretastatin A4 Phosphate Assessed by Anatomic and Carbogen-Based Functional Magnetic Resonance Imaging on Rat Bladder Tumors Implanted in Nude Mice

    Directory of Open Access Journals (Sweden)

    Carole D. Thomas


    Full Text Available Combretastatin A4 phosphate (CA4P causes rapid disruption of the tumor vasculature and is currently being evaluated for antivascular therapy. We describe the initial results obtained with a noninvasive multiparametric magnetic resonance imaging (MRI approach to assess the early effects of CA4P on rat bladder tumors implanted on nude mice. MRI (4.7 T comprised a fast spin-echo sequence for growth curve assessment; a multislice multiecho sequence for T2 measurement before, 15 minutes after, 24 hours after CA4P (100 mg/kg; and a fast T2W* gradient-echo sequence to assess MR signal modification under carbogen breathing before, 35 minutes after, 24 hours after CA4P. The tumor fraction with increased T2W* signal intensity under carbogen (T+ was used to quantify CA4P effect on functional vasculature. CA4P slowed tumor growth over 24 hours and accelerated necrosis development. T+ decrease was observed already at 35 minutes post-CA4P. Early T2 increase was observed in regions becoming necrotic at 24 hours post-CA4P, as confirmed by high T2 and histology. These regions exhibited, under carbogen, a switch from T2W* signal increase before CA4P to a decrease postCA4P. The combination of carbogen-based functional MRI and T2 measurement may be useful for the early follow-up of antivascular therapy without the administration of contrast agents.

  16. Inhaled histamine increases the rate of absorption of sodium cromoglycate from the lung. (United States)

    Richards, R; Fowler, C; Simpson, S; Renwick, A G; Holgate, S T


    Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/- 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways. PMID:1576060

  17. Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone Exposed Offspring (United States)

    Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (ARR) in offspring. To determine if exposure to diesel exhaust during pregnancy worsened postnatal oz...

  18. Increased use of inhaled corticosteroids among young Danish adult asthmatics: An observational study

    DEFF Research Database (Denmark)

    Davidsen, Jesper Rømhild; Søndergaard, Jens; Hallas, Jesper;


    OBJECTIVE: This population-based longitudinal study aimed to investigate trends in use of inhaled corticosteroids (ICS) and determinants of ICS use in young Danish adults with asthma. METHODS: 106 757 users, aged 18-44 years, of anti-asthmatic drugs were identified in the Danish Register of Medical...... Product Statistics during 1997-2006. One year prevalences of ICS use were calculated in categories of gender, age, and annual consumption of inhaled beta-2-agonists (IBA) in defined daily doses (DDD) per year. Determinants of ICS use were estimated by logistic regression models. RESULTS: The one year...... prevalence of ICS use was constant, approximately 64%, during 1997-2000. An annual increase was observed from 67% in 2001 to 77% in 2006. This trend also existed when stratifying on gender, age and IBA use. Using 1997 as baseline, the adjusted odds ratios (ORs) of ICS use in 2000 was 0.98 (95% CI 0...

  19. Increased Non-conducted P-wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats (United States)

    Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that ar...

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

    Directory of Open Access Journals (Sweden)

    Mattheis Kelly


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

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

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


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

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

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


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

  3. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

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    Janssens, Geert O., E-mail: [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Terhaard, Chris H. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Doornaert, Patricia A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Bijl, Hendrik P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Ende, Piet van den [Department of Radiation Oncology, Maastricht University Medical Centre, Maastricht (Netherlands); Chin, Alim [Department of Clinical Oncology, Leiden University Medical Centre, Leiden (Netherlands); Pop, Lucas A.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)


    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  4. Breast tumor oxygenation in response to carbogen intervention assessed simultaneously by three oxygen-sensitive parameters (United States)

    Gu, Yueqing; Bourke, Vincent; Kim, Jae Gwan; Xia, Mengna; Constantinescu, Anca; Mason, Ralph P.; Liu, Hanli


    Three oxygen-sensitive parameters (arterial hemoglobin oxygen saturation SaO2, tumor vascular oxygenated hemoglobin concentration [HbO2], and tumor oxygen tension pO2) were measured simultaneously by three different optical techniques (pulse oximeter, near infrared spectroscopy, and FOXY) to evaluate dynamic responses of breast tumors to carbogen (5% CO2 and 95% O2) intervention. All three parameters displayed similar trends in dynamic response to carbogen challenge, but with different response times. These response times were quantified by the time constants of the exponential fitting curves, revealing the immediate and the fastest response from the arterial SaO2, followed by changes in global tumor vascular [HbO2], and delayed responses for pO2. The consistency of the three oxygen-sensitive parameters demonstrated the ability of NIRS to monitor therapeutic interventions for rat breast tumors in-vivo in real time.

  5. Inhaled Corticosteroids Increase the Risk of Pneumonia in Patients With Chronic Obstructive Pulmonary Disease


    Lee, Ming-Chia; Lee, Chih-Hsin; Chien, Shu-Chen; Chang, Jer-Hwa; She, Han-Lin; Wang, Jann-Yuan; YU, MING-CHIH


    Abstract The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial. From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort). Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables. Among the COPD cohort, those who continuously used ...

  6. High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Bangsbo, Jens


    ) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test...... in systemic concentrations of terbutaline of 23.6 ± 1.1 ng ml(-1) 30 min after administration, and elevated plasma lactate (P = 0.001) and glucose (P = 0.007). MVC was higher for terbutaline than placebo (738 ± 64 vs. 681 ± 68 N) (P = 0.007). In addition, Wingate peak power and mean power were 2.2 ± 0.8 (P...

  7. Inhaled Corticosteroids

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    Peter J. Barnes


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

  8. Adrenal secretion of catecholamines by inhalation of radon water in relation to an increase of the tissue perfusion rate in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Suzuka, Ichio (Okayama Univ. (Japan). School of Medicine)


    To clarify the relationship between the increase in subcutaneous tissue perfusion rate (TPR) upon inhalation of radon water and the vasoactive effects of radon, rabbits inhaled nebulized water containing 14,000-18,000 Bq/1 radon (radon group) taken from Ikeda Mineral Spring, Shimane, Japan. Control rabbits inhaled radon water from the same springs which had been kept for over 10 radon half-life periods. TPR was evaluated 15 minutes after the beginning of inhalation by mass spectrometry. After inhalation for 90 minutes, plasma and adrenal glands were removed, and levels of adrenaline and noradrenaline were analyzed by high-performance liquid chromatography (THI method). Each group was divided into 4 subgroups according to intravenously injected medication as follows: (1) no medication (without adrenergic blocker), (2) phentolamine ([alpha]-blocker), 0.05 mg/kg/min, (3) propranolol (non-selective [beta]-blocker), 1 mg/kg/, and (4) atenolol (selective [beta]-blocker), 6 mg/kg. In the radon group, plasma adrenaline and noradrenaline levels were significantly higher (p<0.01, p<0.05), and adrenal adrenaline and noradrenaline levels were significantly lower (p<0.01, p<0.01) than those in the control group. In the no medication and phentolamine subgroups, TPRs in the radon group were significantly higher than those in the control group (p<0.01, p<0.01). In the propranolol and atenolol subgroups, no significant change of TPR was found. It is suggested that catecholamines are secreted from the adrenal glands upon inhalation of radon water and that the [beta][sub 1]-action of catecholamines contributes to the increase in tissue perfusion. (author).

  9. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats (United States)

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  10. CMTR1 is associated with increased asthma exacerbations in patients taking inhaled corticosteroids

    DEFF Research Database (Denmark)

    Dahlin, Amber; Denny, Joshua; Roden, Dan M


    University Medical Center (VUMC) in Tennessee (369 patients), and Personalized Medicine Research Project (PMRP) at the Marshfield Clinic in Wisconsin (437 patients). Using a case-control study design, the association of each SNP locus with the outcome of asthma exacerbations (defined as asthma...... candidate genes was determined by evaluating an independent microarray expression data set. Our study identified six novel SNPs associated with differential risk of asthma exacerbations (P 1, was associated with an increased risk of exacerbations in both...... populations (OR = 1.07, 95% CI 1.03-1.11; joint P = 2.3 × 10(-06)). Two SNPs (rs2395672 and rs279728) were associated with increased risk of exacerbations, while the remaining four SNPs (rs4271056, rs6467778, rs2691529, and rs9303988) were associated with decreased risk. Three SNPs (rs2395672, rs6467778...

  11. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats. (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S


    The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.

  12. Inhaled Corticosteroids Increase the Risk of Pneumonia in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study. (United States)

    Lee, Ming-Chia; Lee, Chih-Hsin; Chien, Shu-Chen; Chang, Jer-Hwa; She, Han-Lin; Wang, Jann-Yuan; Yu, Ming-Chih


    The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort). Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables. Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort). The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively. In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02-1.11] for per 80 mg of budesonide). Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline. In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE. ICS should be judiciously used in indicated COPD patients.

  13. Acute toxicity profile and compliance to accelerated radiotherapy plus carbogen and nicotinamide for clinical stage T2-4 laryngeal cancer: results of a phase III randomized trial.

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.


    PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with


    NARCIS (Netherlands)

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.


    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with

  15. Inhalation of coriander volatile oil increased anxiolytic-antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1-42) rat model of Alzheimer's disease. (United States)

    Cioanca, Oana; Hritcu, Lucian; Mihasan, Marius; Trifan, Adriana; Hancianu, Monica


    The present study analyzed the possible anxiolytic, antidepressant and antioxidant proprieties of inhaled coriander volatile oil extracted from Coriandrum sativum var. microcarpum in beta-amyloid (1-42) rat model of Alzheimer's disease. The anxiolytic- and antidepressant-like effects of inhaled coriander volatile oil were studied by means of in vivo (elevated plus-maze and forced swimming tests) approaches. Also, the antioxidant activity in the hippocampus was assessed using catalase specific activity and the total content of the reduced glutathione. The beta-amyloid (1-42)-treated rats exhibited the following: decrease of the locomotor activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming and immobility times within forced swimming test. Exposure to coriander volatile oil significantly improved these parameters, suggesting anxiolytic- and antidepressant-like effects. Moreover, coriander volatile oil decreased catalase activity and increased glutathione level in the hippocampus. Our results suggest that multiple exposures to coriander volatile oil can be useful as a mean to counteract anxiety, depression and oxidative stress in Alzheimer's disease conditions.

  16. Current perspectives on the contribution of inhaled corticosteroids to an increased risk for diabetes onset and progression in patients with chronic obstructive pulmonary disease. (United States)

    Herth, Felix J F; Bramlage, Peter; Müller-Wieland, Dirk


    Recent studies have suggested that inhaled corticosteroids (ICS) play a role in the development of hyperglycemia and type-2 diabetes in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, this corticosteroid-associated adverse effect remains controversial. Moreover, the pharmacokinetic properties and patient characteristics that might contribute to an increased risk for diabetes upon ICS exposure have not been thoroughly investigated. In the present review, we critically discuss current evidence regarding the relationship between ICS therapy in COPD patients and an increased risk for the incidence and progression of type-2 diabetes. In addition, we address therapeutic conditions, clinical implications, and future perspectives related to this potentially important ICS-associated adverse effect in COPD patients.

  17. Two-week inhalation of budesonide increases muscle Na,K ATPase content but not endurance in response to terbutaline in men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Jessen, Søren; Onslev, Johan;


    of plasma budesonide, cortisol, and K+. Subjects' performance during cycling to fatigue at 90% of incremental peak power output (iPPO) was measured in response to 4 mg inhaled terbutaline to maximally stimulate Na+,K+ ATPase activity. Plasma concentrations of budesonide rose to 5.0 ± 1.6 n......M with the intervention, whereas no changes were observed in plasma cortisol. Muscle Na+,K+ ATPase content increased (P ≤ 0.01) by 46 ± 34 pmol/(g wet wt) (17% increase) with the intervention. Cycling performance at 90% of iPPO did not change (P = 0.21) with the intervention (203 vs 214 s) in response to terbutaline...


    NARCIS (Netherlands)



    Background - Propranolol inhalation provocation tests are used to measure indirect airways responsiveness in the investigation of asthma. In this study the effects of repeated propranolol inhalation provocation tests within the same day on normal diurnal variation in the forced expiratory volume in

  19. Increased expression of transforming growth factor-β and receptors in primary human airway fibroblasts from chemical inhalation patients.

    Directory of Open Access Journals (Sweden)

    Monireh Sadat Mirzamani


    Full Text Available The widespread use of sulfur mustard  (SM as a chemical warfare agent in the  past century has proved its long-lasting toxic effects. Despite a lot of research over the past decades on Iranian veterans, there are still major gaps in the SM literature. Transforming growth  factor  (TGF-β,  a  cytokine  that  affects  many  different  cell processes,  has  an important role in the lungs of patients with some of chronic airway diseases, especially with respect to airway remodeling in mustard lung.Primary airway fibroblasts from epibronchial biopsies were cultured, and gene expression of TGF-β1, TGF-β2, TbR-I and TbR-II in fibroblasts of SM injured patients and controls were investigated. Expression of TGF-βs and receptors was measured by RT-PCR. Protein level of TGF-β1was surveyed by western blot.Our  findings revealed that expression levels of TGF-β1,  TGF-β2,  TbR-I and TbR-II were upregulated in the  airway fibroblasts of  SM exposed patients  in comparison  with control samples. TGF-β1 expression was shown to be markedly increased in primary lung fibroblasts of chemically injured patients.Our  novel data, suggested that  over-expression of TGF-β  molecule and receptors  in primary airway fibroblasts of mustard gas injured patients may be involved in progression of airway remodeling of these patients.

  20. Zanamivir Oral Inhalation (United States)

    ... for inhaling powder) and five Rotadisks (circular foil blister packs each containing four blisters of medication). Zanamivir powder ... put a hole in or open any medication blister pack until inhaling a dose with the Diskhaler.Carefully ...

  1. Inhalant Abuse and Dextromethorphan. (United States)

    Storck, Michael; Black, Laura; Liddell, Morgan


    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.

  2. Exubera. Inhale therapeutic systems. (United States)

    Bindra, Sanjit; Cefalu, William T


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

  3. Effect of nanopore size distributions on trichloroethylene adsorption and desorption on carbogenic adsorbents

    Energy Technology Data Exchange (ETDEWEB)

    Kane, M.S.; Bushong, J.H.; Foley, H.C. [Univ. of Delaware, Newark, DE (United States); Brendley, W.H. Jr. [Philadelphia Coll. of Textiles, Philadelphia, PA (United States). Dept. of Chemistry


    Two carbon adsorbents, Ambersorb-600 and Ambersorb-563 (A-600 and A-563), were compared for vapor-phase trichloroethylene (TCE) adsorption from humid air streams. These adsorbents retained capacity for TCE in humid environments and were regenerable in situ. Enhanced desorption, and hence, increased working capacities, were achieved with bimodal pore size distributions and hydrophobic surface chemistry. Vapor-phase TCE isotherms confirmed that both of these adsorbents have high capacities for TCE. Only a small difference between the micropore size distributions of A-563 and A-600 was determined by room-temperature methyl chloride adsorption and the modified Horvath-Kawazoe model. Besides differences in particle size and pore volume there was a measurable, but small change, in the fraction of the pores in the ultramicropore range (5 {angstrom} or smaller) of the A-600 adsorbent versus that of A-563. In packed-bed breakthrough curve experiments, A-600 displayed a sharper mass-transfer zone than A-563, but maintained essentially the same capacity for TCE in a humid environment. Both materials were amenable to in-situ regeneration, and the A-600 provided higher overall working capacity than that of A-563.

  4. Biodistribution study of carbogenic dots in cells and in vivo for optical imaging

    Energy Technology Data Exchange (ETDEWEB)

    Li Nan [Shanghai Jiaotong University School of Medicine, Department of Nuclear Medicine, Ruijin Hospital (China); Liang Xiaofei [Shanghai Jiaotong University School of Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital (China); Wang Lili [Shanghai Jiaotong University School of Medicine, Department of Nuclear Medicine, Ruijin Hospital (China); Li Zonghai [Shanghai Jiaotong University School of Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital (China); Li Peiyong, E-mail: [Shanghai Jiaotong University School of Medicine, Department of Nuclear Medicine, Ruijin Hospital (China); Zhu Yihua [East China University of Science and Technology, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering (China); Song Jing [University Hospital for the Albert Einstein College of Medicine, Department of Anesthesiology Montefiore Medical Center (United States)


    Blue fluorescent carbon dots (C-dots) were synthesized and evaluated for their cytotoxicity and also for their optical imaging performance. The results showed that the C-dots could enter into the Hela cells in 15 min incubation and the uptake increased rapidly from 15 min to 2 h. In cytotoxicity study, C-dots were biocompatible and nontoxic to three human cells including two cancer cells (Hela and SMCC-7721) and one normal cell (HEK 293) in concentrations up to 500 {mu}g/mL. Since the endocytic interference factors, including NaN{sub 3}, M{beta}CD, sucrose, and low temperature, could not play an inhibitory effect on C-dots entering into cells, the direct nonendocytic pathway for C-dots was speculated. The C-dots showed encouraging cell-imaging applications in vitro and in vivo. They entered into cells without any further functionalization, and the fluorescence property of these particles can be used for fluorescence-based cell-imaging applications.

  5. Inhalants in Peru. (United States)

    Lerner, R; Ferrando, D


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

  6. Pentamidine Oral Inhalation (United States)

    Pentamidine is an anti-infective agent that helps to treat or prevent pneumonia caused by the organism ... Pentamidine comes as a solution to be inhaled using a nebulizer. It usually is used once every ...

  7. Formoterol Oral Inhalation (United States)

    ... of lung diseases that includes chronic bronchitis and emphysema) in adults. Formoterol inhalation powder is also used with another medication to treat asthma and to prevent breathing difficulties during exercise in ...

  8. Insulin Human Inhalation (United States)

    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 ...

  9. Breath-synchronized plume-control inhaler for pulmonary delivery of fluticasone propionate. (United States)

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


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

  10. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... 260 KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF - 370 KB] Your browser does not ...

  11. Inhaled dust and disease

    Energy Technology Data Exchange (ETDEWEB)

    Holt, P.F.


    This book discusses the following: the respiratory system; respirable dust; the fate of inhaled dust; translocation and some general effects of inhaled dust; silicosis; experimental research on silica-related disease; natural fibrous silicates; asbestos dust levels and dust sources; asbestos-related diseases - asbestosis, lung cancer, mesothelioma and other diseases, cancers at sites other than lung and pleura; experimental research relating to asbestos-related diseases; asbestos hazard - mineral types and hazardous occupations, neighbourhood and domestic hazard; silicates other than asbestos-man-made mineral fibres, mineral silicates and cement; metals; coal mine dust, industrial carbon and arsenic; natural and synthetic organic substances; dusts that provoke allergic alveolitis; tobacco smoke.

  12. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus. (United States)

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


    In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we address the subject of testing new devices before market introduction.

  13. Inhalation anaesthetics and climate change

    DEFF Research Database (Denmark)

    Andersen, Mads Peter Sulbæk; Sander, S P; Nielsen, O J


    Although the increasing abundance of CO(2) in our atmosphere is the main driver of the observed climate change, it is the cumulative effect of all forcing agents that dictate the direction and magnitude of the change, and many smaller contributors are also at play. Isoflurane, desflurane......, and sevoflurane are widely used inhalation anaesthetics. Emissions of these compounds contribute to radiative forcing of climate change. To quantitatively assess the impact of the anaesthetics on the forcing of climate, detailed information on their properties of heat (infrared, IR) absorption and atmospheric...

  14. Estimating the economic consequences of an increased medication adherence due to a potential improvement in the inhaler technique with Spiromax® compared with Turbuhaler® in patients with moderate-to-severe chronic obstructive pulmonary disease in Spain (United States)

    Darbà, Josep; Ramírez, Gabriela; García-Rivero, Juan L; Mayoralas, Sagrario; Pascual, José Francisco; Vargas, Diego; Bijedic, Adi


    Objective The objective of this study was to estimate the economic impact of the introduction of DuoResp® Spiromax®, budesonide/formoterol fixed-dose combination (FDC), focusing on an increase in medication adherence due to an enhancement of the inhalation technique for the treatment of COPD patients in Spain and 5 regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. Methods A 4-year budget impact model was developed for the time period of 2015–2018. This study aimed at evaluating the budget impact associated with the introduction of DuoResp Spiromax in comparison with Symbicort® Turbuhaler® and Rilast® Turbuhaler. National and regional data on COPD prevalence were obtained from the literature. Input data on health care resource utilization were obtained by clinical consultation. Resource included primary care visits, specialist visits, hospitalization, and emergency room visits as well as the length of hospital stay. Based on both pharmacological and health care resource costs, overall annual treatment cost per patient was estimated in EUR 2015. Results It was calculated that 130,777 adults were treated with budesonide/formoterol FDC delivered by a dry powder inhaler, Turbuhaler, in Spain in 2015. However, the target population decreases over the next 4 years. This pattern was observed in 4 regions, but for Andalusia, the treated population increased slightly. The overall budget savings in Spain with the market share of DuoResp Spiromax were estimated to be €6.01 million for the time period of 2015–2018. Region-specific data resulted in savings of €902,133 in Andalusia, €740,520 in Catalonia, €464,281 in Galicia, €748,996 in Madrid, and €495,812 in Valencia for the time period of 2015–2018. Conclusion The introduction of budesonide/formoterol FDC delivered by Spiromax for COPD treatment is likely to contribute in a reduction of health care costs for Spain and in 5 Spanish regions. This model forecasts that Spain and these 5

  15. Estimating the economic consequences of an increased medication adherence due to a potential improvement in the inhaler technique with Spiromax® compared with Turbuhaler® in patients with moderate-to-severe chronic obstructive pulmonary disease in Spain

    Directory of Open Access Journals (Sweden)

    Darbà J


    Full Text Available Josep Darbà,1 Gabriela Ramírez,2 Juan L García-Rivero,3 Sagrario Mayoralas,4 José Francisco Pascual,5 Diego Vargas,6 Adi Bijedic7 1Department of Economics, Universitat de Barcelona, 2BCN Health Economics & Outcomes Research S.L., Barcelona, 3Hospital Laredo, Cantabria, 4Hospital Ramón y Cajal, Madrid, 5Hospital General Universitario de Alicante, Alicante, 6Hospital de Alta Resolución el Toyo, Andalusia, 7Market Access and HEOR Department, TEVA Pharmaceutical, Madrid, Spain Objective: The objective of this study was to estimate the economic impact of the introduction of DuoResp® Spiromax®, budesonide/formoterol fixed-dose combination (FDC, focusing on an increase in medication adherence due to an enhancement of the inhalation technique for the treatment of COPD patients in Spain and 5 regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia.Methods: A 4-year budget impact model was developed for the time period of 2015–2018. This study aimed at evaluating the budget impact associated with the introduction of DuoResp Spiromax in comparison with Symbicort® Turbuhaler® and Rilast® Turbuhaler. National and regional data on COPD prevalence were obtained from the literature. Input data on health care resource utilization were obtained by clinical consultation. Resource included primary care visits, specialist visits, hospitalization, and emergency room visits as well as the length of hospital stay. Based on both pharmacological and health care resource costs, overall annual treatment cost per patient was estimated in EUR 2015. Results: It was calculated that 130,777 adults were treated with budesonide/formoterol FDC delivered by a dry powder inhaler, Turbuhaler, in Spain in 2015. However, the target population decreases over the next 4 years. This pattern was observed in 4 regions, but for Andalusia, the treated population increased slightly. The overall budget savings in Spain with the market share of DuoResp Spiromax were

  16. [Inhaled corticosteroids for COPD

    NARCIS (Netherlands)

    Dekhuijzen, P.N.R.


    Over 60% of patients with COPD are treated with inhaled corticosteroids (ICS), even though their use is still subject to debate. The inflammatory process in the lungs of patients with COPD is dominated by macrophages, CD8+ T-lymphocytes, neutrophilic granulocytes and mast cells, as well as an increa

  17. Inhalants. Specialized Information Service. (United States)

    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…

  18. Inhalational Lung Disease

    Directory of Open Access Journals (Sweden)

    S Kowsarian


    Full Text Available Inhalational lung diseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lung diseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become apparent several years after exposure to the particles. However, for certain types of dusts, e.g., silicone dioxide crystal and beryllium, heavy exposure within a short period can cause an acute disease. Pulmonary involvement in asbestosis is usually in the lower lobes. On the contrary, in silicosis and coal worker pneumoconiosis, the upper lobes are involved predominantly. For imaging evaluation of pneumoconiosis, high-resolution computed tomography (CT is superior to conventional chest x-ray. Magnetic resonance imaging (MRI and positron emission tomography (PET scan are helpful in those with suspected tumoral lesions. In this essay, we reviewed the imaging aspects of inhalational lung disease.

  19. Behavioral changes in mice following benzene inhalation. (United States)

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


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

  20. Ozone inhalation modifies the rat liver proteome

    Directory of Open Access Journals (Sweden)

    Whitney S. Theis


    Full Text Available 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.

  1. Effect of 4% lidocaine inhalation in bronchial asthma. (United States)

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


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

  2. [Ventricular fibrillation following deodorant spray inhalation]. (United States)

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


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

  3. Hepatotoxic Alterations Induced by Inhalation of Trichloroethylene (TCE) in Rats

    Institute of Scientific and Technical Information of China (English)


    Objective Trichloroethylene (TCE) is one of the most potent organic unsaturated solvents being used in dry cleaning, metal degreasing, thinner for paints varnishes and electroplating, etc. and has been reported to be a hepatotoxicant through oral and dermal exposure. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation toxicity study was carried out for hepatotoxic studies. Method Inhalation toxicity studies was carried out by exposing rats to TCE for 8, 12 and 24 weeks in a dynamically operated whole body inhalation chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results Significant increase in liver weight (liver enlargement) appearance of necrotic lesions with fatty changes and marked necrosis were observed after longer duration (12 and 24 weeks) of TCE exposure. The lysosomal rupture resulted in increased activity of acid and alkaline phosphatase alongwith reduced glutathione content and total increased sulfhydryl content in liver tissue. Conclusion TCE exposure through Inhalation route induces hepatotoxicity in terms of marked necrosis with fatty changes and by modulating the lysosomal enzymes.

  4. Inhaled insulin--does it become reality? (United States)

    Siekmeier, R; Scheuch, G


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

  5. Inhalation delivery of asthma drugs. (United States)

    Matthys, H


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

  6. Intestinal circulation during inhalation anesthesia

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  7. Insulin inhalation for diabetic patients: Nursing considerations

    Directory of Open Access Journals (Sweden)

    Hanan Mohammed Mohammed


    Full Text Available Scientific knowledge has advanced to enable the development of inhaled insulin. It is a form of diabetes medication administered via the pulmonary system that studies have shown to be efficacious in the treatment of both type 1 and type 2 diabetes. Inhaled insulin is a new, safe means to deliver insulin that may increase patient compliance with insulin therapy, helping them to achieve optimal glycemic control and possibly reducing their risk of developing cardiovascular complications. However, diabetes is a chronic illness requiring lifetime intervention. Empowering patients with the knowledge of the diabetes disease process may give them the confidence to be more autonomous in managing their diabetes. HIIP gives nurse practitioners a new option that may improve their patients’ acceptance of insulin therapy, and improve glycemic control.

  8. Fluticasone and Vilanterol Oral Inhalation (United States)

    ... the inhaler without using your dose, you will waste the medication. The counter will count down by ... it from the foil overwrap or after every blister has been used (when the dose indicator reads ...

  9. Potent Inhalational Anesthetics for Dentistry. (United States)

    Satuito, Mary; Tom, James


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

  10. [Evoked potentials and inhalation anesthetics]. (United States)

    Thiel, A; Russ, W; Hempelmann, G


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

  11. Evaluating inhaler use technique in COPD patients

    Directory of Open Access Journals (Sweden)

    Pothirat C


    to incorrect technique (adjusted odds ratio 4.1, 95% CI 1.2–13.4, P=0.022. Formal training resulted in a statistically significant decrease in percentage of incorrect techniques for all devices and for the pMDI (59.4% vs 48.6%, P<0.001; 72.4% vs 48.3%, P=0.039, respectively.Conclusion: Inhalation technique in COPD patients without face-to-face training was mostly unsatisfactory, especially in patients with low education levels. The Handihaler was the inhaler device associated with the lowest technique failure. Face-to-face inhalation technique training significantly increased technique compliance for the pMDI. Keywords: chronic obstructive pulmonary disease, inhalation, technique, compliance

  12. Zinc toxicology following particulate inhalation

    Directory of Open Access Journals (Sweden)

    Cooper Ross


    Full Text Available 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.

  13. Inhaler Costs and Medication Nonadherence Among Seniors With Chronic Pulmonary Disease (United States)

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


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

  14. Inhalant Abuse: Is Your Child at Risk? (United States)

    ... can be valuable as well. With help, your child can end inhalant abuse and learn how to make healthy choices for a lifetime. References Baydala L. Inhalant abuse. Paediatrics and Child Health. 2010;15:443. Results from the 2013 ...

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

    Directory of Open Access Journals (Sweden)

    Valerie Chan


    Full Text Available 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.

  16. Sudden death due to inhalant abuse in youth: Case report

    Directory of Open Access Journals (Sweden)

    Ramazan Akcan


    Full Text Available Intentional inhalation or abuse of volatile substances is a common public health problem all over the world. As these substances generate euphoria frequency of use among adolescents and young adults is increasing steadily. In cases using inhalants to achieve a euphoric state -without knowing possible consequences- sudden death may occurdue to acute cardio-pulmonary dysfunction.Here we present a case of sudden death of a nineteen-year-old female due to inhalation of volatile from butane containing lighter gas tube, with the findings of autopsy and death scene investigation.In the context of this case; it was aimed to draw attention to the risk of sudden death and steady increase of frequencyof volatile substance abuse among adolescents and young adults due to various psycho-social factors.

  17. Age dependent systemic exposure to inhaled salbutamol

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans


    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

  18. [Health significance of inhaled particles]. (United States)

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


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

  19. Parental Influence on Inhalant Use (United States)

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


    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…

  20. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    DEFF Research Database (Denmark)

    Saber, Anne T.; Jacobsen, Nicklas R.; Jackson, Petra


    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction...... epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk...

  1. Impact of inhalation therapy on oral health

    Directory of Open Access Journals (Sweden)

    Navneet Godara


    Full Text Available 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.

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


    Zanen, A L; Rietveld, A. P.


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

  3. The role of disposable inhalers in pulmonary drug delivery

    NARCIS (Netherlands)

    de Boer, Anne H; Hagedoorn, Paul


    Introduction: There is increasing interest in the pulmonary route for both local and systemically acting drugs, vaccines and diagnostics and new applications may require new inhaler technology to obtain the most therapeutically and/or cost-effective administration. Some of these new applications can

  4. Inhalation therapy in children with asthma. (United States)

    Brand, P L


    Current consensus guidelines advocate the use of inhalation therapy for all children with asthma. In this paper, the published evidence on technical and practical aspects of inhalation therapy in children with asthma is reviewed. For children under 6 yr of age, nebulizers and metered dose inhaler (MDI)/spacer combinations can be used. Nebulizers are cumbersome, bulky, and difficult to operate. They require technical and hygienic maintenance. A number of studies has shown that nebulizers are no more effective in delivering bronchodilator therapy than MDI/spacer combinations. Thus, for young children with asthma, MDI/spacer combinations are the device of choice for inhalation therapy. Due to static charge, the output from plastic spacers is lower than that from metal spacers. Static charge on plastic spacers can be reduced by washing the spacer in detergent and allow it to drip dry. Most children aged 6 yr or over can use a dry powder inhaler (DPI) reliably. Modern DPIs require relatively low inspiratory flow rates for proper operation. Lung deposition from the Turbuhaler is twice as high as that from the Diskus, but the former device is slightly more difficult to operate than the latter. Many children with asthma have a poor inhalation technique. Because a reliable inhalation technique is the key to successful inhalation therapy, inhalation technique should be instructed carefully and checked repeatedly in every asthmatic child using an inhaler device.

  5. Inhalation therapy in mechanical ventilation (United States)

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


    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

  6. Passive inhalation of cannabis smoke

    Energy Technology Data Exchange (ETDEWEB)

    Law, B.; Mason, P.A.; Moffat, A.C.; King, L.J.; Marks, V.


    Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 liter), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analyzed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

  7. Inhalational and dermal exposures during spray application of biocides. (United States)

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


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

  8. [Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti-infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris 2012]. (United States)

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


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

  9. AB034. Comparative effectiveness of prescribing similarversusdissimilar inhalers for COPD therapy (United States)

    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


    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

  10. Use of inhaled corticosteroids in pediatric asthma

    DEFF Research Database (Denmark)

    Bisgaard, H


    Inhaled corticosteroids reduce asthma symptoms and exacerbations, improve lung function, and reduce airway inflammation and bronchial hyperreactivity more effectively than other treatments. However, inhaled corticosteroids may be unable to return lung function and bronchial hyperreactivity...... of the disease. Therefore, a change in treatment strategy toward earlier introduction of corticosteroids may impede airway remodeling, bronchial hyperreactivity, and airway damage. No other treatment has been found to affect the course of the disease. Systemic side-effects, particularly inhibition of growth...... in asthmatic children using inhaled corticosteroids, do not seem to be cause for concern. Growth retardation has not been reported when inhaled corticosteroid doses of

  11. Wildlife ecological screening levels for inhalation of volatile organic chemicals. (United States)

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


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

  12. Treatment of chronic rhinosinusitis with pressure-pulsed corticosteroid inhalation. (United States)

    Goektas, Oender; Lau, Larissa; Olze, Heidi


    Chronic rhinosinusitis may cause olfactory dysfunction and affects quality of life in patients. In a prospective study we investigated the effect of topical application of corticosteroids through pressure-pulsed inhalation as treatment option of chronic rhinosinusitis with olfactory disorder. Patients with sinonasal olfactory disorder according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) were allocated to the new nasal inhalation therapy or a systemic corticosteroid therapy, each receiving a corticosteroid course of 12 days. 18 patients received topical corticosteroid pressure-pulsed inhalation (AMSA, Schumacher, Dausenau) and 15 systemic corticosteroid. Olfactory function was measured before and after treatment using the Threshold Discrimination Identification score (TDI score) and visual analogue scales. Lund Mackay score (LMS) was measured before starting treatment. Olfactory function (OF) increased from 17.5 ± 6.4 to 21 ± 7.9 TDI points (p treatment after 2 months. In the follow-up period of 6 months, the mean TDI score dropped to 20.0 ± 9.2 points (p = 0.01). There was no correlation between LMS and TDI. Treatment of chronic rhinosinusitis with pressure-pulsed inhalation was demonstrated to be effective. Multicenter investigations with large participant numbers are needed.

  13. Inhalation and dermal exposure among asphalt paving workers. (United States)

    McClean, M D; Rinehart, R D; Ngo, L; Eisen, E A; Kelsey, K T; Herrick, R F


    The primary objective of this study was to identify determinants of inhalation and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving workers. The study population included three groups of highway construction workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside construction workers who did not work with hot-mix asphalt. During multiple consecutive work shifts, personal air samples were collected from each worker's breathing zone using a Teflon filter and cassette holder connected in series with an XAD-2 sorbent tube, while dermal patch samples were collected from the underside of each worker's wrist. All exposure samples were analyzed for PACs, pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures varied significantly by task, crew, recycled asphalt product (RAP) and work rate (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold increase in inhalation PAC exposures and a 2-fold increase in dermal PAC exposure, compared with low RAP mix. The inhalation PAC exposures were consistent with the workers' proximity to the primary source of asphalt fume (paver operators > screedmen > rakers > roller operators), such that the adjusted mean exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP) were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0 microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to which the workers have actual contact with asphalt-contaminated surfaces (rakers > screedmen > paver operators > roller operators), such that the adjusted mean exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65 ng/cm2, high RAP). Paving task, RAP content and crew were also found to be significant determinants of

  14. Therapeutic application of inhaled nitric oxide in adult cardiac surgical patients. (United States)

    Makker, Robina; Mehta, Yatin; Trehan, Naresh; Bapna, Rk


    Increased pulmonary vascular resistance can be detrimental to the cardiac output in post-operative cardiac surgical patients. Pulmonary vasodilator therapy by systemic pharmacologic agents is non-selective. Inhaled nitric oxide is a selective pulmonary vasodilator and does not cause systemic hypotension. In this prospective study, 14 adult post-operative cardiac surgical patients with pulmonary hypertension underwent inhaled nitric oxide therapy and their hemodynamic changes were evaluated. Inhaled nitric oxide was administered in doses of 5 ppm-25 ppm. The result was a decrease in pulmonary vascular resistance from 456.57 +/- 137.13 to 357.64 +/- 119.80 dynes-sec- Continued. - See Free Full Text.

  15. Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome (United States)

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


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

  16. Inhalable PEGylated Phospholipid Nanocarriers and PEGylated Therapeutics for Respiratory Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers

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    Priya Muralidharan


    Full Text Available Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEGylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols.

  17. Investigation of inhalation anthrax case, United States. (United States)

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


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

  18. Clinical effectiveness of the Respimat® inhaler device in managing chronic obstructive pulmonary disease: evidence when compared with other handheld inhaler devices

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    et al


    only outcome for which data were available for meta-analysis was exacerbations, which were not significantly different (RR 1.20: P = 0.12. In addition, five trials with 2136 patients showed that there was no difference in risk of exacerbations or nasopharyngitis when Respimat was compared with all other handheld inhaler devices (RR 1.18: P = 0.13 and RR 1.33: P = 0.19, respectively. None of the clinical outcome measures reported was significantly different when the same, higher, or lower doses of medication were used in the inhaler devices being compared. Unfortunately, none of the included trials reported mortality as an outcome measure.Conclusions: Evidence from high-quality trials published to date suggests that the Respimat inhaler does not provide any additional clinical benefit to that provided by other inhaler devices in the management of COPD. Although in vitro studies have reported differences between the Respimat inhaler device and other handheld devices, we found no difference in any clinical outcome measures, including lung function and adverse events. Although recent reports have highlighted concerns of increased mortality with the Respimat inhaler device, none of the included trials reported mortality as an outcome. Only a small number of trials reported data that could be used in this systematic review, and a limited number of studies have been published that compare Respimat with other inhaler devices using the same drug and strength. Therefore, further trials comparing Respimat with other handheld inhaler devices using the same drug and dose are required before firm conclusions can be drawn. The concern with increased mortality with Respimat use should be investigated urgently.Keywords: Respimat, aerosol cloud, handheld inhaler devices, COPD

  19. Inhalable desert dust, urban emissions, and potentially biotoxic metals in urban Saharan-Sahelian air (United States)

    Garrison, Virginia H.; Majewski, Michael S.; Konde, Lassana; Wolf, Ruth E.; Otto, Richard D.; Tsuneoka, Yutaka


    Saharan dust incursions and particulates emitted from human activities degrade air quality throughout West Africa, especially in the rapidly expanding urban centers in the region. Particulate matter (PM) that can be inhaled is strongly associated with increased incidence of and mortality from cardiovascular and respiratory diseases and cancer. Air samples collected in the capital of a Saharan–Sahelian country (Bamako, Mali) between September 2012 and July 2013 were found to contain inhalable PM concentrations that exceeded World Health Organization (WHO) and US Environmental Protection Agency (USEPA) PM2.5 and PM10 24-h limits 58 – 98% of days and European Union (EU) PM10 24-h limit 98% of days. Mean concentrations were 1.2-to-4.5 fold greater than existing limits. Inhalable PM was enriched in transition metals, known to produce reactive oxygen species and initiate the inflammatory response, and other potentially bioactive and biotoxic metals/metalloids. Eroded mineral dust composed the bulk of inhalable PM, whereas most enriched metals/metalloids were likely emitted from oil combustion, biomass burning, refuse incineration, vehicle traffic, and mining activities. Human exposure to inhalable PM and associated metals/metalloids over 24-h was estimated. The findings indicate that inhalable PM in the Sahara–Sahel region may present a threat to human health, especially in urban areas with greater inhalable PM and transition metal exposure.

  20. Toxicological Assessment of Noxious Inhalants

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    Kleinsasser, N. H.


    Full Text Available 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.

  1. Inhalant Dependence and its Medical Consequences

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    Mehmet Hamid Boztaş


    Full Text Available The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in adults working in substance existing places. Inhalant usage is common in disadvantaged groups, children living in street, people with history of crimes, prison, depression, suicide, antisocial attitudes and conflict of family, history of abuse, violence and any other drug dependence and isolated populations. Inhalants are absorbed from lungs, after performing their quick and short effect metabolized by cytochrom P450 enzyme system except inhalant nitrites group which has a depressing effect like alcohol. In chronic use general atrophy, ventricular dilatation and wide sulcus were shown in cerebrum, cerebellum and pons by monitoring brain. Defects are mostly in periventricular, subcortical regions and in white matter. Demyelinization, hyperintensity, callosal slimming and wearing off in white and gray matter margins was also found. Ravages of brain shown by brain monitorisation are more and serious in inhalant dependence than in other dependences. It is important to decrease use of inhalants. Different approaches should be used for subcultures and groups in prevention. Prohibiting all the matters including inhalant is not practical as there are too many substances including inhalants. Etiquettes showing harmful materials can be used but this approach can also lead the children and adolescents recognize these substances easily.. Despite determintal effects of inhalant dependence, there are not yet sufficient number of studies conducted on prevention and

  2. Inhalants (United States)

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

  3. Inhalants (United States)

    ... and Over-the-Counter Medications Stimulant ADHD Medications: Methylphenidate and Amphetamines Synthetic Cannabinoids Synthetic Cathinones ("Bath Salts") Effects of Drug Abuse Comorbidity: Addiction and Other Mental Disorders Drug Use ...

  4. Inhalants (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Health Effects Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  5. Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype (United States)

    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...

  6. Adhesion forces in interactive mixtures for dry powder inhalers--evaluation of a new measuring method. (United States)

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


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

  7. [New technical developments for inhaled sedation]. (United States)

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


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

  8. Total Intravenous Versus Inhalation Anesthesia in Patients Undergoing Laparoscopic Cholecystectomies. Effects on Two Proinflammatory Cytokines Serum Levels: Il-32 and TNF-Alfa.

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    Hadade Adina


    Full Text Available Introduction: It has been reported that as compared with total intravenous anesthesia (TIVA, inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.

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

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    Yi-fan LIU


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

  10. Inhaler device preferences in older adults with chronic lung disease

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    Ghazala L


    Full Text Available Introduction: Patient preferences are important for medication adherence and patient satisfaction, but little is known about older adult preferences for inhaler devices. Methods: We developed a 25-item written self-administered questionnaire assessing experience with inhalers, prior inhaler education, and preferences with respect to inhaler device features and inhaler device teaching. We then conducted a cross-sectional survey of patients at least 65 years of age with chronic lung disease who had experience using inhaler devices for at least six months in the ambulatory setting. Results: Fifty participants completed the questionnaire. The majority of participants (80% reported prior experience with a metered dose inhaler (MDI, but only 26% used an MDI with a spacer. Most patients (76% had received formal instruction regarding proper use of the inhaler, but only 34% had ever been asked to demonstrate their inhaler technique. Physician recommendation for an inhaler, cost of the inhaler device, and inhaler features related to convenience were important with respect to patient preferences. With regard to inhaler education, participants prefer verbal instruction and/or hands-on demonstration at the time a new inhaler is prescribed in the setting of the prescribing provider’s office. Conclusion: Patient preferences for inhaler devices and inhaler education among older adults indicate physician recommendation, cost, and convenience are important. The impact of patient preferences on inhaler adherence and clinical outcomes remains unknown.

  11. Persistent increases in inflammatory cytokines, Akt, and MAPK/ERK pathways after inhalation exposure of rats to Libby amphibole (LA) or amosite: comparison to effects after intratracheal exposure to LA or naturally occurring asbestos. (United States)

    Human exposure to LA and other mined or processed asbestos increases risk of lung inflammation, fibrosis, and cancer. Health risks from exposure to naturally occurring asbestos (NOA) are not as well-understood. Mechanisms of long-term toxicity were compared in male F344 rats expo...

  12. Inhalation devices and patient interface: human factors. (United States)

    Leiner, Stefan; Parkins, David; Lastow, Orest


    The development of any inhalation product that does not consider the patient needs will fail. The needs of the patients must be identified and aligned with engineering options and physical laws to achieve a robust and intuitive-to-use inhaler. A close interaction between development disciplines and real-use evaluations in clinical studies or in human factor studies is suggested. The same holds true when a marketed product needs to be changed. Caution is warranted if an inhaler change leads to a change in the way the patient handles the device. Finally, the article points out potential problems if many inhaler designs are available. Do they confuse the patients? Can patients recall the correct handling of each inhaler they use? How large is the risk that different inhaler designs pose to the public health? The presentations were given at the Orlando Inhalation Conference: Approaches in International Regulation co-organised by the University of Florida and the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) in March 2014.

  13. Emerging inhaled bronchodilators: an update. (United States)

    Cazzola, M; Matera, M G


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



    Sibila, Oriol; Anzueto, Antonio; Restrepo, Marcos I.


    Community-acquired pneumonia (CAP) is the leading infectious cause of death in developed countries. Several studies have shown that the risk of pneumonia is increased in patients with Chronic Obstructive Pulmonary Disease (COPD) who are receiving chronic inhaled corticosteroids (ICS). The impact of ICS On pneumonia prognosis is controversial. Recent studies have shown that COPD patients with prior ICS use have less mortality after developing CAP as compared with patients with COPD without pri...

  15. Quantitative analysis of dynamic airway changes after methacholine and salbutamol inhalation on xenon-enhanced chest CT

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    Park, Sang Joon; Goo, Jin Mo; Kim, Jong Hyo; Park, Eun-Ah [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Lee, Chang Hyun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Radiation Medicine, Medical Research Center, Seoul (Korea, Republic of); Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Jung, Jae-Woo; Park, Heung-Woo [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of); Cho, Sang-Heon [Seoul National University Hospital, Healthcare Gangnam Center, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University College of Medicine, Institute of Allergy and Clinical Immunology, Seoul (Korea, Republic of)


    To investigate the dynamic changes in airways in response to methacholine and salbutamol inhalation and to correlate the xenon ventilation index on xenon-enhanced chest CTs in asthmatics. Thirty-one non-smokers (6 normal, 25 asthmatics) underwent xenon-enhanced chest CT and pulmonary function tests. Images were obtained at three stages (basal state, after methacholine inhalation and after salbutamol inhalation), and the total xenon ventilation index (TXVI) as well as airway values were measured and calculated. The repeated measures ANOVA and Spearman's correlation coefficient were used for statistical analysis. TXVI in the normal group did not significantly change (P > 0.05) with methacholine and salbutamol. For asthmatics, however, the TXVI significantly decreased after methacholine inhalation and increased after salbutamol inhalation (P < 0.05). Of the airway parameters, the airway inner area (IA) significantly increased after salbutamol inhalation in all airways (P < 0.01) in asthmatics. Airway IA, wall thickness and wall area percentage did not significantly decrease after methacholine inhalation (P > 0.05). IA of the large airways was well correlated with basal TXVI, FEV{sub 1} and FVC (P < 0.05). Airway IA is the most reliable parameter for reflecting the dynamic changes after methacholine and salbutamol inhalation, and correlates well with TXVI in asthmatics on xenon-enhanced CT. (orig.)

  16. Inhaled beclomethasone in pregnant asthmatic women--a systematic review. (United States)

    de Aguiar, M M; da Silva, H J; Rizzo, J Â; Leite, D F B; Silva Lima, M E P L; Sarinho, E S C


    The aim of this study was to systematically review the safety and efficacy of inhaled beclomethasone for asthma treatment in pregnant women. We performed a systematic review in Medline, LILACS and SciELO electronic databases in December 2012. A total of 3433 articles were found by using the keywords asthma, pregnancy and beclomethasone. Among these, 1666 were from Medline, via PubMed, and 1767 were from LILACS and SciELO. Nine of these articles were selected. Only one paper suggested an increased foetal risk for congenital malformations, and one other for offspring endocrine and metabolic disturbances. Data are mostly reassuring, supporting the use of glucocorticoid inhalants during pregnancy, and we found no evidence of inferiority in relation to efficacy and safety of beclomethasone compared to other drugs used in pregnant asthmatic women.

  17. Inhaled insulin for controlling blood glucose in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Bernard L Silverman


    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  18. Subchronic inhalation toxicity of gold nanoparticles

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    Chung Yong


    Full Text Available Abstract 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

  19. Simple and scalable method for peptide inhalable powder production. (United States)

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


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

  20. Inhalation anthrax in a home craftsman. (United States)

    Suffin, S C; Carnes, W H; Kaufmann, A F


    Inhalation anthrax with complicating subarachnoid hemorrhage due to simultaneous infection with two capsular biotypes of Bacillus anthracis of different virulence for the mouse is reported. The patient, a home craftsman, acquired his infection from imported animal-origin yarn.

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... avoid an attack by taking your medicine exactly as your doctor or other medical professional tells you ... keep them with your Asthma Action Plan. Using a metered dose inhaler with a spacer Your browser ...

  2. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... among persons with active asthma Use of long-term control medication among persons with active asthma Uncontrolled ...

  3. Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats. (United States)

    Watanabe, Sadahiro; Fujita, Masanori; Ishihara, Masayuki; Tachibana, Shoichi; Yamamoto, Yoritsuna; Kaji, Tatsumi; Kawauchi, Toshio; Kanatani, Yasuhiro


    The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2(')-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG.

  4. Inhaler devices - from theory to practice

    DEFF Research Database (Denmark)

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


    This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...... and the difficulties patients face. Provision of short, clear instructions with demonstration of critical steps and checking technique during later clinical visits are necessary if these aerosolised medications are to be fully beneficial....

  5. Inhalation anesthesia. What to learn from modelisation? (United States)

    Deriaz, H


    Models describing pharmacokinetics of inhalational anesthetic agents have been developed, usually on Mapleson's description of the body as a collection of tissues characterised by their volume, local blood flow and anesthetic solubility. Such models are very useful to understand the use of inhalation agents and circle circuit, to compare consumption of different agents in different anesthetic practices, and to prepare the anesthetist to administer new products safely.

  6. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans. (United States)

    Johnson, Matthew W; MacLean, Katherine A; Caspers, Michael J; Prisinzano, Thomas E; Griffiths, Roland R


    Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

  7. Atomization method for verifying size effects of inhalable particles on lung damage of mice. (United States)

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


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

  8. Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert


    Full Text Available Abstract Inhaled prostanoids and phosphodiesterase (PDE inhibitors have been suggested for treatment of severe pulmonary hypertension. In catheterized rabbits with acute pulmonary hypertension induced by continuous infusion of the stable thromboxane analogue U46619, we asked whether sildenafil (PDE1/5/6 inhibitor, motapizone (PDE3 inhibitor or 8-Methoxymethyl-IBMX (PDE1 inhibitor synergize with inhaled iloprost. Inhalation of iloprost caused a transient pulmonary artery pressure decline, levelling off within per se ineffective dose of each PDE inhibitor (200 μg/kg × min 8-Methoxymethyl-IBMX, 1 μg/kg × min sildenafil, 5 μg/kg × min motapizone with subsequent iloprost nebulization, marked amplification of the prostanoid induced pulmonary vasodilatory response was noted and the area under the curve of PPA reduction was nearly threefold increased with all approaches, as compared to sole iloprost administration. Further amplification was achieved with the combination of inhaled iloprost with sildenafil plus motapizone, but not with sildenafil plus 8MM-IBMX. Systemic hemodynamics and gas exchange were not altered for all combinations. We conclude that co-administration of minute systemic doses of selective PDE inhibitors with inhaled iloprost markedly enhances and prolongs the pulmonary vasodilatory response to inhaled iloprost, with maintenance of pulmonary selectivity and ventilation perfusion matching. The prominent effect of sildenafil may be operative via both PDE1 and PDE5, and is further enhanced by co-application of a PDE3 inhibitor.

  9. Effect of inhaled procaterol on cough receptor sensitivity to capsaicin in patients with asthma or chronic bronchitis and in normal subjects.


    Fujimura, M; Sakamoto, S.; Kamio, Y.; Bando, T.; Kurashima, K.; T. Matsuda


    BACKGROUND--To evaluate the effect of inhaled beta 2 adrenergic agonists on the sensitivity of airway cough receptors, the effect of inhaled procaterol on cough induced by aerosolised capsaicin, a stimulant of C fibres, was studied in patients with asthma or chronic bronchitis and in normal subjects. METHOD--Eleven patients with asthma and 10 with chronic bronchitis and 14 normal subjects participated. Increasing concentrations of capsaicin solution were inhaled for 15 seconds by tidal breath...

  10. Influence of inhaler technique on asthma and COPD control: a multicenter experience (United States)

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


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

  11. The effects of abused inhalants on mouse behavior in an elevated plus-maze. (United States)

    Bowen, S E; Wiley, J L; Balster, R L


    Previous research has shown that abused inhalants (i.e., the volatile solvents) share some of the pharmacological properties of drugs used in the treatment of anxiety. In an attempt to further examine commonalities in the effects of inhalants and central nervous system depressant drugs, the behavioral effects of inhaled 1,1,1-trichloroethane, toluene, methoxyflurane and the convulsant vapor flurothyl were examined and compared to those of diazepam in the elevated plus-maze, a test used to predict antianxiety effects. After inhalant exposure or diazepam injection, mice were placed in the center of an elevated plus-maze and the number of entries and time spent in each type of arm (open versus closed) were measured during 5-min tests. Exposure to increasing concentrations of toluene produced concentration-related increases in the total number of open arm entries and the total time spent on the open arms, a pattern of behavioral effects similar to that produced by diazepam. A similar pattern was observed for increasing concentrations of 1,1,1-trichloroethane and methoxyflurane but changes in open arm activity were only observed at concentrations that increased locomotor activity. Conversely, only decreases in open arm time and number of entries were observed for flurothyl. The increasing evidence for commonalities in the behavioral effects of volatile solvents and depressant drugs may provide a foundation for understanding the neurobehavioral basis of inhalant abuse.

  12. Assessment of inhalation dose sensitivity by physicochemical properties of airborne particulates containing naturally occurring radioactive materials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Si Young; Choi, Cheol Kyu; Kim, Yong Geon; Choi, Won Chul; Kim, Kwang Pyo [Kyung Hee University, Seoul (Korea, Republic of)


    Facilities processing raw materials containing naturally occurring radioactive materials (NORM) may give rise to enhanced radiation dose to workers due to chronic inhalation of airborne particulates. Internal radiation dose due to particulate inhalation varies depending on particulate properties, including size, shape, density, and absorption type. The objective of the present study was to assess inhalation dose sensitivity to physicochemical properties of airborne particulates. Committed effective doses to workers resulting from inhalation of airborne particulates were calculated based on International Commission on Radiological Protection 66 human respiratory tract model. Inhalation dose generally increased with decreasing particulate size. Committed effective doses due to inhalation of 0.01μm sized particulates were higher than doses due to 100μm sized particulates by factors of about 100 and 50 for {sup 238}U and {sup 230}Th, respectively. Inhalation dose increased with decreasing shape factor. Shape factors of 1 and 2 resulted in dose difference by about 18 %. Inhalation dose increased with particulate mass density. Particulate mass densities of 11 g·cm{sup -3} and 0.7 g·cm{sup -3} resulted in dose difference by about 60 %. For {sup 238}U, inhalation doses were higher for absorption type of S, M, and F in that sequence. Committed effective dose for absorption type S of {sup 238}U was about 9 times higher than dose for absorption F. For {sup 230}Th, inhalation doses were higher for absorption type of F, M, and S in that sequence. Committed effective dose for absorption type F of {sup 230}Th was about 16 times higher than dose for absorption S. Consequently, use of default values for particulate properties without consideration of site specific physiochemical properties may potentially skew radiation dose estimates to unrealistic values up to 1-2 orders of magnitude. For this reason, it is highly recommended to consider site specific working materials and

  13. Adhesive mixtures for inhalation : the cohesion between formulation variables, inhalation variables and dispersion performance

    NARCIS (Netherlands)

    Grasmeijer, Floris


    Powdery drugs for inhalation to treat asthma and COPD are often mixed with lactose to enable their accurate dosing. However, because the drug particles adhere strongly to the lactose particles, they are difficult to disperse with the aid of a dry powder inhaler. As a result, over half the dose usual

  14. Conference report: 2nd Medicon Valley Inhalation Symposium. (United States)

    Lastow, Orest


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

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

    Directory of Open Access Journals (Sweden)

    Peter Brand


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

  16. Assessing inhalation injury in the emergency room

    Directory of Open Access Journals (Sweden)

    Tanizaki S


    Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: 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. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

  17. Sevoflurane: a new inhalational anesthetic agent. (United States)

    Wallin, R F; Regan, B M; Napoli, M D; Stern, I J


    Laboratory screening of a series of halogenated methyl isopropyl ethers revealed sevoflurane (fluoromethyl-1,1,1,3,3,3,-hexafluroro-2-propyl ether) as a potent nonexplosive inhalational anesthetic agent. Sevoflurance, a pleasant-smelling liquid, boils at 58.5 degrees C at 760 torr and has a vapor pressure of 200 torr at 25 degrees C. It is nonflammable in air and has lower flammability limits of 11 vols percent in O2 and 10 vols percent in N2O. Sevoflurane exhibits limited chemical reactivity in vitro; it is subject to slight but measurable hydrolysis, and reacts with soda lime to form traces of related ethers. It provides rapid anesthetic induction and recovery consistent with its low distribution coefficients (blood:gas, 0.6; corn oil:gas, 41.6; olive oil:gas, 53.4). In dogs, anesthetic concentrations of sevoflurane did not produce spontaneous cardiac arrhythmias and did not sensitize the heart to epinephrine. Electroencephalographic patterns were similar to those observed during anesthesia with halothane. In rats, small increases in the urinary excretion of inorganic fluoride ion occurred during the first 24 hours after anesthesia. Subacute studies in dogs and rats, using closed-circle absorption with soda lime, revealed no toxicologically significant changes in animals anesthetized frequently for 2 weeks. Sevoflurane appears to be a unique volatile anesthetic agent worthy of further study.

  18. Translocation pathways for inhaled asbestos fibers

    Directory of Open Access Journals (Sweden)

    Mantegazza F


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

  19. Cardiovascular morbidity and the use of inhaled bronchodilators

    Directory of Open Access Journals (Sweden)

    Christine Macie


    Full Text Available Christine Macie, Kate Wooldrage, Jure Manfreda, Nicholas AnthonisenDepartment of Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaAbstract: We used the Manitoba Health database to examine the relationship between use of inhaled respiratory drugs in people with chronic obstructive respiratory diseases and cardiovascular hospitalizations from 1996 through 2000. The drugs examined were beta agonists [BA], ipratropium bromide IB, and inhaled steroids (ICS. End points were first hospitalizations for supraventricular tachycardia, myocardial infarction, heart failure or stroke. A nested case control analysis was employed comparing people with and without cardiovascular events. Cases and controls were matched for gender and age, and conditional logistic regression was used in multivariate analysis considering other respiratory drugs, respiratory diagnosis and visit frequency, non-respiratory, non-cardiac comorbidities, and receipt of drugs for cardiovascular disease. In univariate analyses, BA, IB and ICS were all associated with hospitalizations for cardiovascular disease, but in multivariate analyses ICS did not increase risk while both BA and IB did. There were interactions between respiratory and cardiac drugs receipt in that bronchodilator associated risks were higher in people not taking cardiac drugs; this was especially true for stroke. There were strong interactions with specific cardiac drugs; for example, both BA and IB substantially increased the risk of supraventricular tachycardia in patients not anti-arryhthmic agents, but not in the presence of such agents. We conclude that bronchodilator therapy for chronic obstructive diseases is associated with increased cardiovascular risk, especially in patients without previous cardiovascular diagnoses, and that this is unlikely due to the severity of the respiratory disease, since risk was not increased with ICS.Keywords: bronchodilator therapy, inhaled corticosteroids, nested case

  20. Use of inhaled corticosteroids in pediatric asthma

    DEFF Research Database (Denmark)

    Bisgaard, H


    Inhaled corticosteroids reduce asthma symptoms and exacerbations, improve lung function, and reduce airway inflammation and bronchial hyperreactivity more effectively than other treatments. However, inhaled corticosteroids may be unable to return lung function and bronchial hyperreactivity...... to normal when introduced for moderately severe asthma. This finding highlights the need to improve treatment strategy in pediatric asthma. The natural progression of persistent asthma may lead to loss of lung function and chronic bronchial hyperreactivity for children and adults. There is evidence...... to suggest that asthma acts via a chronic inflammatory process that causes remodeling of the airways with mucosal thickening and smooth muscle hypertrophy. An optimal treatment strategy would be one aimed at reducing the ongoing airway inflammation. Inhaled steroids ameliorate the inflammation, whereas...

  1. IRIS Toxicological Review of Ammonia - Noncancer Inhalation (Final Report) (United States)

    The U.S. Environmental Protection Agency's (USEPA) has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammon...

  2. Cow Dung Ingestion and Inhalation Dependence: A Case Report (United States)

    Khairkar, Praveen; Tiple, Prashant; Bang, Govind


    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.

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

    DEFF Research Database (Denmark)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven;


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

  4. Anxiolytic-like effects of inhaled linalool oxide in experimental mouse anxiety models. (United States)

    Souto-Maior, Flávia Negromonte; de Carvalho, Fabíola Lélis; de Morais, Liana Clébia Soares Lima; Netto, Sueli Mendonça; de Sousa, Damião Pergentino; de Almeida, Reinaldo Nóbrega


    Linalool oxide is a monoterpene that is found in some species of aromatic plants. The effects of the inhalation of linalool oxide (0.65%, 1.25%, 2.5% and 5.0% w/w) in the elevated plus-maze and light/dark box tests as animal models of anxiety were investigated in adult male mice and compared with the effects of the reference anxiolytic diazepam (0.5 and 2.0 mg/kg), administered intraperitoneally. Additionally, the effects of inhaled linalool oxide were investigated in the rotarod test. Linalool oxide significantly increased the number of visits to the open arms of the elevated plus-maze and the amount of time spent there as well as the total number of entries. In the light/dark box test, inhalation of linalool oxide led to an increase in the time spent by the mice in the brightly-lit chamber and in the number of times the animal crossed from one compartment to another. Performance on the rotarod was unaffected. Thus, inhaled linalool oxide was found to have anxiolytic properties in both animal models, without causing any motor deficit. These results suggest that inhalation of linalool oxide may be a useful means of counteracting anxiety.

  5. Inhaled Carbon Nanotubes Reach the Sub-Pleural Tissue in Mice (United States)

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


    Summary Carbon nanotubes have fibre-like shape1 and stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice2, raising concerns that inhaled nanotubes3 may cause pleural fibrosis and/or mesothelioma4. Here we show that multi-walled carbon nanotubes reach the sub-pleura in mice after a single inhalation exposure of 30 mg/m3 for 6 hours. Nanotubes were embedded in the sub-pleural wall and within sub-pleural 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. Sub-pleural fibrosis increased after 2 and 6 weeks following inhalation. None of these effects were seen in mice that inhaled carbon black nanoparticles or a lower dose of nanotubes (1 mg/m3). This work advances a growing literature on pulmonary toxicology of nanotubes5 and suggests that minimizing inhalation of nanotubes during handling is prudent until further long term assessments are conducted. PMID:19893520

  6. Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation. (United States)

    Koul, Ashwani; Bala, Shashi; Yasmeen; Arora, Neha


    This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action.

  7. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury (United States)

    Zhang, Fan; Li, Mian-yang; Lan, Ya-ting; Wang, Cheng-bin


    T helper (Th) 17 cells and CD4+ CD25+ regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID:26884314

  8. A simple pharmacokinetic method to evaluate the pulmonary dose in clinical practice--analyses of inhaled sodium cromoglycate. (United States)

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


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

  9. Ubiquitin and stromal cell-derived factor-1α in bronchoalveolar lavage fluid after burn and inhalation injury. (United States)

    Baker, Todd A; Davis, Christopher S; Bach, Harold H; Romero, Jacqueline; Burnham, Ellen L; Kovacs, Elizabeth J; Gamelli, Richard L; Majetschak, Matthias


    The objective of the study was to determine whether the CXC chemokine receptor (CXCR) 4 ligands ubiquitin and stromal cell-derived factor (SDF)-1α are detectable in bronchoalveolar lavage fluid (BALF) after burn and inhalation injury and whether their concentrations in BALF are associated with injury severity, physiological variables, or clinical outcomes. BALF was obtained on hospital admission from 51 patients (48 ± 18 years) with burn (TBSA: 23 ± 24%) and inhalation injury (controls: 10 healthy volunteers, 42 ± 8 years). BALF was analyzed for total protein and for ubiquitin and SDF-1α by enzyme-linked immunosorbent assay. Ubiquitin/SDF-1α levels were normalized to total BALF protein content. The extent of inhalation injury was determined during bronchoscopy using a standardized scoring system. Percent TBSA, Baux scores, revised Baux scores, and clinical variables were documented. Ubiquitin and SDF-1α were detectable in 40% of normal BALF specimens. After injury, ubiquitin was detectable in 90% (P patients (P burn and inhalation injury. Increases in BALF ubiquitin after inhalation injury may maintain CXCR4-mediated lung protection and repair processes. The finding that BALF ubiquitin decreased with higher grades of inhalation injury may provide a biological correlate for an insufficient local inflammatory response after severe inhalation injury.

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

    Directory of Open Access Journals (Sweden)

    Roggeri A


    Full Text Available Alessandro Roggeri,1 Claudio Micheletto,2 Daniela Paola Roggeri1 1ProCure Solutions, Nembro, Bergamo, Italy, 2Respiratory Unit, Mater Salutis Hospital, Legnago, Verona, Italy 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

  11. Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

    Energy Technology Data Exchange (ETDEWEB)

    Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others


    Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

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

    NARCIS (Netherlands)

    Vincken, W.; Dekhuijzen, P.N.R.; Barnes, P.


    For patients with COPD, inhalation is the preferred route of administration of respiratory drugs for both maintenance and acute treatment. Numerous inhaler types and devices have been developed, each with their own particularities, advantages and disadvantages. Nevertheless, published COPD managemen

  13. 49 CFR 172.555 - POISON INHALATION HAZARD placard. (United States)


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

  14. 49 CFR 172.429 - POISON INHALATION HAZARD label. (United States)


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

  15. 42 CFR 84.90 - Breathing resistance test; inhalation. (United States)


    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; inhalation. 84.90...-Contained Breathing Apparatus § 84.90 Breathing resistance test; inhalation. (a) Resistance to inhalation airflow will be measured in the facepiece or mouthpiece while the apparatus is operated by a...

  16. Latex Allergy with Discus Form of Inhalation Drug of Asthma

    Directory of Open Access Journals (Sweden)

    Ogun Sezer


    Full Text Available The prevalence of latex allergy in healthcare workers and which was taken chronic medical therapy has significantly increased during the last 15 years. Latex allergy generally refers to a type 1 reaction to natural rubber latex (NRL proteins with clinical manifestations ranging from contact urticaria to asthma and anaphylaxis. In this report, we discuss latex allergy with discus form of inhalation drug of asthma after contact of discus form to lips. Still, latex allergy is an important problem in patients with latex allergy. We must inform all patients about latex allergy and all latex containing devices. [TAF Prev Med Bull 2009; 8(5.000: 451-452

  17. Effects of inspiratory resistance, inhaled beta-agonists and histamine on canine tracheal blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, W.T.; Baile, E.M.; Brancatisano, A.; Pare, P.D.; Engel, L.A. (Dept. of Respiratory Medicine, Westmead Hospital, Westmead, NSW (Australia))


    Tracheobronchial blood flow is potentially important in asthma as it could either influence the clearance of mediators form the airways, thus affecting the duration and severity of bronchoispasm, or enhance oedema formation with a resultant increase in airflow obstruction. In anaesthetized dogs, spontaneously breathing via a tracheostomy, we investigated the effects of three interventions which are relevant to acute asthma attacks and could potentially influence blood flow and its distribution to the mucosa and remaining tissues of the trachea: (1) increased negative intrathoracic pressure swings (-25[+-]1 cmH[sub 2]O) induced by an inspiratory resistance; (2) variable inhaled doses of a beta-adrenoceptor-agonist (terbutaline); and (3) aerosolized histamine sufficient to produce a threefold increase in pulmonary resistance. Microspheres labelled with different radioisotopes were used to measure blood flow. Resistive breathing did not influence tracheobronchial blood flow. Following a large dose of terbutaline, mucosal blood flow (Qmb) increased by 50%. After inhaled histamine, Qmb reached 265% of the baseline value. We conclude that, whereas increased negative pressure swings do not influence tracheobronchial blood flow or its distribution, inhalation of aerosolized terbutaline, corresponding to a conventionally nebulized dose, increases mucosal blood flow. Our results also confirm that inhaled histamine, in a dose sufficient to produce moderate bronchoconstriction, increases tracheal mucosal blood flow in the area of deposition. (au).

  18. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma

    DEFF Research Database (Denmark)

    Bisgaard, H; Klug, B; Sumby, B S;


    The study aimed to investigate dose consistency and particle distribution from the dry powder inhalers Diskus and Turbuhaler. Full profiles of inhalation pressure versus time were recorded in 18 4 yr old and 18 8 yr old asthmatic children through Diskus and Turbuhaler inhalers. These data were used...... is a determinant of the quality of the aerosol. The mean (SD) amount of drug in large particles (>4.7 microm), fine particles (children and 71 (3), 18 (2) and 2...... (1) from the 8 yr old children, respectively. Similar particle fractions from the Budesonide Turbuhaler were 35 (9), 21 (10) and 7 (5) from 4 yr old children and 30 (7), 32 (9) and 12 (6) from 8 yr old children. In conclusion, the Diskus inhaler provides an improved dose consistency through...

  19. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

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


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

  20. Pneumonitis after Inhalation of Mercury Vapours

    Directory of Open Access Journals (Sweden)

    JD Glezos


    Full Text Available A 43-year-old man presented to hospital with pneumonia but only after discharge from hospital did he admit to deliberate prior inhalation of mercury. His pulmonary involvement appeared to resolve almost completely with antibiotics and supportive care. Nevertheless, persisting elevated urinary excretion of mercury required two courses of chelation therapy. No serious systemic sequelae were observed.

  1. Dry powder inhalers for pulmonary drug delivery

    NARCIS (Netherlands)

    Frijlink, H.W.; De Boer, A.H.


    The pulmonary route is an interesting route for drug administration, both for effective local therapy (asthma, chronic obstructive pulmonary disease or cystic fibrosis) and for the systemic administration of drugs (e.g., peptides and proteins). Well-designed dry powder inhalers are highly efficient

  2. Inhaled sodium cromoglycate for asthma in children

    NARCIS (Netherlands)

    van der Wouden, Johannes C.; Uijen, Johannes H. J. M.; Bernsen, Roos M. D.; Tasche, Marjolein J. A.; de Jongste, Johan C.; Ducharme, Francine


    Background Sodium cromoglycate has been recommended as maintenance treatment for childhood asthma for many years. Its use has decreased since 1990, when inhaled corticosteroids became popular, but it is still used in many countries. Objectives To determine the efficacy of sodium cromoglycate compare

  3. Inhaled corticosteroids do not affect behaviour

    NARCIS (Netherlands)

    de Vries, T. W.; van Roon, E. N.; Duiverman, E. J.


    Aim: To determine whether children with asthma and on inhaled corticosteroids have more behavioural problems, such as aggressiveness and hyperactivity, as compared with healthy controls and with children under medical care because of other disorders. Methods: Questionnaires were given to three group

  4. Inhalation drug delivery devices: technology update

    Directory of Open Access Journals (Sweden)

    Ibrahim M


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

  5. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, V.J.; Arts, J.H.E.; Kuper, C.F.; Slootweg, P.J.; Woutersen, R.A.


    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and me

  6. Computational modelling for dry-powder inhalers

    NARCIS (Netherlands)

    Kröger, Ralf; Woolhouse, Robert; Becker, Michael; Wachtel, Herbert; de Boer, Anne; Horner, Marc


    Computational fluid dynamics (CFD) is a simulation tool used for modelling powder flow through inhalers to allow optimisation both of device design and drug powder. Here, Ralf Kröger, Consulting Senior CFD Engineer, ANSYS Germany GmbH; Marc Horner, Lead Technical Services Engineer, Healthcare, ANSYS

  7. Inhalant Use in Latina Early Adolescent Girls (United States)

    Guzmán, Bianca L.; Kouyoumdjian, Claudia


    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…

  8. Neurological impacts from inhalation of pollutants and the nose-brain connection. (United States)

    Lucchini, R G; Dorman, D C; Elder, A; Veronesi, B


    The effects of inhaled particles have focused heavily on the respiratory and cardiovascular systems. Most studies have focused on inhaled metals, whereas less information is available for other particle types regarding the effects on the brain and other extra-pulmonary organs. We review here the key available literature on nanoparticle uptake and transport through the olfactory pathway, the experimental data from animal and in vitro studies, and human epidemiological observations. Nanoparticles (brain from the respiratory tract via sensory neurons and transport from the distal alveoli into the blood or lymph as free particles or inside phagocytic cells. These mechanisms and subsequent biologic responses may be influenced by the chemical composition of inhaled particles. Animal studies with ambient particulate matter and certain other particles show alterations in neuro-inflammatory markers of oxidative stress and central neurodegeneration. Human observations indicate motor, cognitive, and behavioral changes especially after particulate metal exposure in children. Exposure to co-pollutants and/or underlying disease states could also impact both the biokinetics and effects of airborne particles in the brain. Data are needed from the areas of inhalation, neurology, and metal toxicology in experimental and human studies after inhalation exposure. An increased understanding of the neurotoxicity associated with air pollution exposure is critical to protect susceptible individuals in the workplace and the general population.

  9. Effects of nitric oxide inhalation on pulmonary serial vascular resistances in ARDS. (United States)

    Rossetti, M; Guénard, H; Gabinski, C


    The pulmonary vasculature site of action of nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) is still unknown. Seven patients were studied during the early stage of ARDS. The bedside pulmonary artery single-occlusion technique, which allows estimation of the pulmonary capillary pressure (Pcap) and segmental pulmonary vascular resistance, was used without NO or with increasing inhaled NO concentrations (15 and 25 parts per million [ppm]). Systemic circulatory parameters remained unaltered during 15 ppm NO inhalation, whereas 25 ppm NO inhalation slightly decreased mean systemic arterial pressure from 76.7 +/- 5.1 (mean +/- SEM) to 69 +/- 5.2 mm Hg (p resistance decreased by 28% (p resistance of the capillary-venous compartment fell during 25 ppm NO inhalation from 100 +/- 16 to 47 +/- 16 dyn x s x m(2) x cm(-5) (p resistance was unchanged. In these patients NO inhalation during the early stage of ARDS reduces selectively Ppam and Pcapm by decreasing the pulmonary capillary-venous resistance. This latter effect may reduce the filtration through the capillary bed and hence alveolar edema during ARDS.

  10. Radon inhalation protects mice from carbon-tetrachloride-induced hepatic and renal damage. (United States)

    Kataoka, Takahiro; Nishiyama, Yuichi; Toyota, Teruaki; Yoshimoto, Masaaki; Sakoda, Akihiro; Ishimori, Yuu; Aoyama, Yutaka; Taguchi, Takehito; Yamaoka, Kiyonori


    We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl(4)-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

  11. Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalation. (United States)

    Aswania, Osama; Chrystyn, Henry


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

  12. Workplace Inhalant Abuse in Adult Female: Brief Report

    Directory of Open Access Journals (Sweden)

    Rohit Verma


    Full Text Available Inhalant abuse is the purposeful inhalation of intoxicating gases and vapors for the purpose of achieving an altered mental state. With its propensity for being yet an under-recognized form of substance use, being gateway to hard substances, cross-cultural penetration crossing socioeconomic boundaries, and causing significant morbidity and mortality in early ages, the prevention of inhalant misuse is a highly pertinent issue. This clinical report identifies a newer perspective in the emergence of inhalant abuse initiation. We report a case of an adult female with late onset of inhalant dependence developing at workplace and recommend for greater awareness, prevention, and management of this expanding substance abuse problem.

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

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


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

  14. Incident pneumonia and mortality in patients with chronic obstructive pulmonary disease. A double effect of inhaled corticosteroids? (United States)

    Festic, Emir; Scanlon, Paul D


    Inhaled corticosteroids are commonly prescribed for patients with severe chronic obstructive pulmonary disease. Although their use improves quality of life and reduces exacerbations, it is associated with increased risk of pneumonia. Curiously, their use has not been associated with increased risk of pneumonia-related or overall mortality. We review pertinent literature to further explore the effects of inhaled corticosteroids on incident pneumonia and mortality in patients with chronic obstructive pulmonary disease. The association of use of inhaled corticosteroids and incident pneumonia is substantial and has been present in the majority of the studies on the topic. This includes both randomized controlled trials and observational studies. However, all of the studies have substantial risk of bias. Most randomized trials are limited by lack of systematic ascertainment of pneumonia; they depended on adverse event reporting. Many observational studies included proper radiographic assessment of pneumonia, but they are limited by their retrospective, observational design. The unadjusted higher risk of pneumonia is associated with longer duration of use, more potent ICS compounds, and higher doses. That implies a dose-effect relationship. Unlike pneumonia, mortality is a precise outcome. Despite the robust association of inhaled corticosteroid use with increased risk of pneumonia, all studies find either no difference or a reduction in pulmonary-related and overall mortality associated with the use of inhaled corticosteroids. These observations suggest a double effect of inhaled corticosteroids (i.e., an adverse effect plus an unexplained mitigating effect).

  15. Effect of nitric oxide inhalation on gas exchange in acute severe pneumonia. (United States)

    Gómez, Federico P; Amado, Veronica M; Roca, Josep; Torres, Antoni; Nicolas, Josep M; Rodriguez-Roisin, Robert; Barberà, Joan A


    Inhaled nitric oxide (NO) causes selective pulmonary vasodilatation and may improve gas exchange. The study was aimed to evaluate the acute effects of inhaled NO on pulmonary gas exchange in severe unilateral pneumonia, where hypoxemia results from increased intrapulmonary shunt. We studied 8 patients without preexisting lung disease (59±18 yr; 4M/4F) with early unilateral severe pneumonia and respiratory failure. Pulmonary and systemic hemodynamics and gas exchange, including ventilation-perfusion (V;A/Q;) distributions, were measured at baseline and while breathing 5 and 40 parts per million (ppm) of NO. Inhaled NO caused a dose-dependent fall in pulmonary vascular resistance (by 12% and 21%, with 5 and 40ppm, respectively; ppneumonia.

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

    Directory of Open Access Journals (Sweden)

    Patricia Green MD


    Full Text Available 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.

  17. Smoke-inhalation injury and the effect of carbon monoxide in the sheep model

    Energy Technology Data Exchange (ETDEWEB)

    Shimazu, T.; Ikeuchi, H.; Hubbard, G.B.; Langlinais, P.C.; Mason, A.D.


    The role of carbon monoxide (CO) in causing the physiologic and anatomic changes characteristic of smoke inhalation injury was evaluated in 34 sheep. The smoke-exposed group received a dose of smoke known to produce mild inhalation injury. The CO group received a pure gas mixture that contained concentrations of oxygen, carbon dioxide, and CO similar to those in the smoke. Cardiopulmonary function was measured immediately after exposure, and 24 and 72 hours after exposure. The CO group showed a transient increase in cardiac output, but the smoke group showed no such response. The CO group maintained normal PaO2 levels during the 72-hour study period; the smoke group gradually developed hypoxemia. The lungs of the CO exposed animals had no discernible histologic changes. These results indicate that CO per se is not the primary etiologic agent of smoke inhalation injury.

  18. [Teratologic cranio-encephalic effects of chronic thinner inhalation in progenitors, in rats and humans]. (United States)

    Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M


    Inhalation of thinner by youngsters and adolescents is an increasing drug abuse problem in Mexico. It presents serious repercussions upon socio-economic, cultural, legal and health (neurologic and psychiatric) problems. We report a comparative study in humans and rats which demonstrate the embryotoxic and craneo encephalic teratologic effects in the children and brood of progenitors who have chronically inhaled thinner (in the case of pregnant women, before, at the beginning and throughout pregnancy). Inhaled thinner passes directly to the blood stream and crosses the placentary barrier freely reaching the embryo. It may cause craneal bone and partial or total encephalon agenesia, added to macro and microscopic lesions secondary to direct aggression to the neuroepithelial germ cells. Abortions and premature labor with weight and size underdeveloped products and placentary hemorrhages occur. Usually these die, but if they survive they show trascendental mental retardation, as well as neurologic and psychiatric sequels.

  19. 46. Micronuclei induced by chronical treatment of SO2 inhalation in mouse bone marrow cells

    Institute of Scientific and Technical Information of China (English)


    In the chronical experiment of treating with sulfur dioxide(SO2) inhalation, Micronuclei(MN) frequencies in the polychromatophilic erythroblasts(PCE) of mouse bone marrow and the frequencies of cells with MN were significantly increased in dose-dependent manner. There is a significant difference between the male and the female animals. The results also showed that SO2 inhibited urethone-induced MN formation, it is a antagonistic joint action to Urethone. These results furtherly confirm that SO2 inhalation is a clastogenetic and genotoxic agent to mammalian cells, and the combination roles of SO2 and other mutagens are complexity.

  20. Tablet and inhaled controller medication refill frequencies in children with asthma. (United States)

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


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

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

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


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

  2. Sputum inflammation predicts exacerbations after cessation of inhaled corticosteroids in COPD

    NARCIS (Netherlands)

    Liesker, Jeroen J. W.; Bathoorn, Erik; Postma, Dirkje S.; Vonk, Judith M.; Timens, Wim; Kerstjens, Huib A. M.


    Introduction: The GOLD guidelines advocate not to institute inhaled corticosteroids (ICS) in patients with mild-to-moderate COPD. However, many patients do use ICS and in some patients, withdrawal is associated with deteriorating lung function and increased exacerbation rates. Unfortunately, physici

  3. Toxicological Assessments of Rats Exposed Prenatally to Inhaled Vapors of Gasoline and Gasoline-Ethanol Blends (United States)

    The primary alternative to petroleum-based fuels is ethanol, which is blended with gasoline in the United States at concentrations up to 15% for most automobiles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ...

  4. Nasal aerodynamics protects brain and lung from inhaled dust in subterranean diggers, Ellobius talpinus

    NARCIS (Netherlands)

    M.P. Moshkin; D.V. Petrovski; A.E. Akulov; A.V. Romashchenko; L.A. Gerlinskaya; V.L. Ganimedov; M.I. Muchnaya; A.S. Sadovsky; I.V. Koptyug; A.A. Savelov; S. Yu Troitsky; Y.M. Moshkn; V.I. Bukhtiyarov; N.A. Kolchanov; R.Z. Sagdeev; V.M. Fomin


    textabstractInhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols


    Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted...

  6. Interspecies modeling of inhaled particle deposition patterns

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  7. Inhaled medicinal cannabis and the immunocompromised patient. (United States)

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


    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.

  8. Acute myocardial involvement after heroin inhalation

    Directory of Open Access Journals (Sweden)

    Ritu Karoli


    Full Text Available Amongst the illicit drugs cocaine, amphetamines and cannabis have been studied and documented well to cause myocardial infarction by different mechanisms but there is very sparse data available on myocardial involvement after heroin abuse. We report a young man who developed acute myocardial injury after heroin inhalation and alcohol binge drinking. Heroin induced cardio toxic effect and vasospasm compounded by alcohol were suspected to be the cause of this.

  9. Electrostatics in pharmaceutical aerosols for inhalation. (United States)

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


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

  10. Oxidative stress effects of thinner inhalation



    Thinners are chemical mixtures used as industrial solvents. Humans can come into contact with thinner by occupational exposure or by intentional inhalation abuse. Thinner sniffing causes damage to the brain, kidney, liver, lung, and reproductive system. We discuss some proposed mechanism by which thinner induces damage. Recently, the induction of oxidative stress has been suggested as a possible mechanism of damage. This paper reviews the current evidence for oxidative stress effects induced ...

  11. Inflammatory Mediators in Smoke Inhalation Injury (United States)


    of arte- rial oxygen to the fraction of inspired oxygen ( PFR ) until a certain “threshold” smoke dose has been delivered; thereaf- ter, decreases in... PFR are steep [11, 16]. Pathologically, these models demonstrate evidence of tracheal and lobar bronchial mucosal sloughing with pseudomembrane...during an inhalation injury [31]. Initial animal research on six sheep given intravenous heparin improved PFR , improved peak airway pressures and

  12. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta). (United States)

    Chang, Steve W C; Barter, Joseph W; Ebitz, R Becket; Watson, Karli K; Platt, Michael L


    People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone synthesized by hypothalamic neurons in the mammalian brain, can enhance affiliation or boost exclusion in different species in distinct contexts, belying any simple mechanistic neural model. Here we show that inhaled OT penetrates the CNS and subsequently enhances the sensitivity of rhesus macaques to rewards occurring to others as well as themselves. Roughly 2 h after inhaling OT, monkeys increased the frequency of prosocial choices associated with reward to another monkey when the alternative was to reward no one. OT also increased attention to the recipient monkey as well as the time it took to render such a decision. In contrast, within the first 2 h following inhalation, OT increased selfish choices associated with delivery of reward to self over a reward to the other monkey, without affecting attention or decision latency. Despite the differences in species typical social behavior, exogenous, inhaled OT causally promotes social donation behavior in rhesus monkeys, as it does in more egalitarian and monogamous ones, like prairie voles and humans, when there is no perceived cost to self. These findings potentially implicate shared neural mechanisms.

  13. [Effect of mixing of fine carrier particles on dry powder inhalation property of salbutamol sulfate (SS)]. (United States)

    Iida, K; Leuenberger, H; Fueg, L M; Müller-Walz, R; Okamoto, H; Danjo, K


    The most commonly used formulations for dry powder inhalations are binary ordered mixes composed of micronized drugs and coarse carriers. An optimal dry powder aerosol formulation should possess an optimal inhalation property and a good flow property. These characteristics are especially important for a multidose dry powder inheler (DPI). In the present study, model powder blend were prepared consisting of synthesized sugar (different particle sized isomalt; IM-PF, IM-FS, IM-F) as a carrier and micronized salbutamol sulfate (SS). These ordered mixtures were aerosolized by the multidose JAGO DPI (SkyePharma AG) and in vitro deposition properties (fine particle fraction, FPF) were evaluated by a twin impinger (TI) at a flow rate of 60 l/min. The separation property between SS and carrier particles was investigated by the centrifuge method and air jet sieve (AJS) method. It was found that FPF decreased with increasing carrier particle size. However, a large carrier particle possesses a good flow property. Therefore, the effect of mixing of fine carrier particles (IM-PF) into the large carrier particles (IM-FS) on dry powder inhalation property was investigated. When the proportion of IM-PF (fine carrier) increase from 0% to 25% of the total carrier powder blend, the FPF also increases from 16.7% to 38.9%. It is concluded that the effect of mixing of fine carrier particles might be a suitable method for improving the dry powder inhalation properties.

  14. The future of combining inhaled drugs for COPD. (United States)

    Bjerg, Anders; Lundbäck, Bo; Lötvall, Jan


    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality globally, and its prevalence is projected to continue to increase owing to trends in smoking. Treatment of COPD has evolved from the initial adaptations of drugs and treatment strategies successfully used in asthma into more specific pharmacological strategies following global guidelines. Bronchodilating anticholinergic and beta-2-stimulating agents and anti-inflammatory corticosteroid drugs delivered by inhalators are the mainstay of COPD treatment. Despite significant progress, current pharmacotherapies neither fully alleviate the airway obstruction in COPD, nor reverse the progressive nature of the disease. This review discusses inhalation therapies which have recently become clinically available or are being developed, with focus on combination therapies. There is accumulating evidence that the combination of two or all three drug classes, triple therapy, is superior to single drug therapy. Several fixed combinations of both currently available and novel molecules will be launched for clinical use within the next few years. Also, improved understanding of subgroups within the clinical spectrum of COPD, is likely to offer new potentials to improve COPD care.

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

    Directory of Open Access Journals (Sweden)

    Dudvarski Ilic A


    third visit compared to the first one, as measured by the seven-step inhaler usage score (5.94 and 6.82, respectively; P<0.001. Improvement of disease control significantly increased from visit 1 to visit 2 (53.9% and 74.5%, respectively; P<0.001 and from visit 2 to visit 3 (74.5% and 77%, respectively; P<0.001. Patients’ subjective assessment of symptoms and quality of life significantly improved from visit 1 to visit 3 (P<0.001.Conclusion: Adherence to inhalation therapy is one of the key factors of successful respiratory disease treatment. Therefore, health care professionals should insist on educational programs aimed at improving patients’ inhalation technique with different devices, resulting in better long-term disease control and improved quality of life. Keywords: Turbuhaler, adherence, inhalation technique, asthma, COPD

  16. The nasal distribution of metered dose inhalers. (United States)

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


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

  17. Inhalation cancer risk assessment of cobalt metal. (United States)

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


    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.

  18. Effects of prolonged inhalation of silica and olivine dusts on immune functions in the mouse. [Escherichia coli; Staphylococcus

    Energy Technology Data Exchange (ETDEWEB)

    Scheuchenzuber, W.J.; Eskew, M.L.; Zarkower, A.


    Immunologic responses determined in Balb/c mice following intermittent silica or olivine inhalations for 150, 300, or 570 days. Animals dust-exposed for 570 days were tested immediately postexposure, while those exposed for 150 or 300 days were tested immediately or were rested for 30 or 150 days as a measure of possible recovery from effects of the dust inhalations. Silica inhalation suppressed the number of specific plaque-forming cells (PFC) in the spleen produced in response to aerosolized Escherichia coli bacteria. When tested after 570 days, silica inhalation also reduced the ability of alveolar marcophages to phagocytize Staphylococcus auerus in vitro. Olivine inhalation also suppressed splenic PFCs and alveolar macrophage phagocytosis, but to a lesser degree than silica. In animals tested after 570 days of dust exposure, it was determined that the ability to lyse allogeneic tumor cells in vitro was impaired by olivine slightly more than by silica, while antibody-dependent cell-mediated cytotoxic and mitogenic responses by splenic lymphocytes were unchanged by inhalation of either dust. The effects of increased exposure periods, and of recovery periods after exposure, were confounded by age-related immunologic changes which were present after the longer exposures.

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

    Directory of Open Access Journals (Sweden)

    Min Seo


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

  20. Spatial distribution of respirable and inhalable particulate matter concentration in sawmills of South-South Region of Nigeria

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    T.F. Ediagbonya


    Full Text Available Dust particles in the air that can be respired into the nose or mouth during normal breathing are known as inhalable particle. Inhalation decreases gradually with increasing particle diameter. The respirable and inhalable sawdust were collected from nine different sawmills in Benin City from November 2009 to February 2010 using portable programmable SKC Air Check XR5000 High Volume Gravimetric Sampler Model 210-5000 Serial No. 20537 and I.O.M (Institute Occupational Medicine Edinburg Multi dust sampler, Batch No. 221442/1. The objective of this study is to know the concentration of inhalable suspended particulate matter fraction and the respirable suspended particulate matter fraction in sawmill particulate. The mean concentration range of the respirable suspended particulate matter was 173.61-520.83 g/m3 and the inhalable suspended particulate matter was in a range of 555.56-2,013.98 g/m3. A strong positive correlation existed for inhalable suspended particulate matter and respirable suspended particulate matter. And the spatial variation was significant and remarkable.

  1. Hepatotoxic Alterations Induced by Subchronic Exposure of Rats to Formulated Fenvalerate (20% EC) by Nose Only Inhalation

    Institute of Scientific and Technical Information of China (English)



    Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. Method Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. Conclusion The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.

  2. Influence of Binasal and Uninasal Inhalations of Essential Oil of Abies koreana Twigs on Electroencephalographic Activity of Human (United States)

    Seo, Min; Sowndhararajan, Kandhasamy


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

  3. Oral and inhaled corticosteroids: Differences in P-glycoprotein (ABCB1) mediated efflux

    Energy Technology Data Exchange (ETDEWEB)

    Crowe, Andrew, E-mail:; Tan, Ai May


    There is concern that P-glycoprotein mediated efflux contributes to steroid resistance. Therefore, this study examined bidirectional corticosteroid transport and induction capabilities for P-glycoprotein (P-gp) to understand which of the systemic and inhaled corticosteroids interacted with P-gp to the greatest extent. Hydrocortisone, prednisolone, prednisone, methylprednisolone, and dexamethasone represented systemically active drugs, while fluticasone propionate, beclomethasone dipropionate, ciclesonide and budesonide represented inhaled corticosteroids. Aldosterone and fludrocortisone represented mineralocorticoids. All drugs were detected using individually optimised HPLC protocols. Transport studies were conducted through Caco-2 monolayers. Hydrocortisone and aldosterone had efflux ratios below 1.5, while prednisone showed a P-gp mediated efflux ratio of only 1.8 compared to its active drug, prednisolone, with an efflux ratio of 4.5. Dexamethasone and beclomethasone had efflux ratios of 2.1 and 3.3 respectively, while this increased to 5.1 for methylprednisolone. Fluticasone showed an efflux ratio of 2.3. Protein expression studies suggested that all of the inhaled corticosteroids were able to induce P-gp expression, from 1.6 to 2 times control levels. Most of the systemic corticosteroids had higher passive permeability (> 20 × 10{sup −6} cm/s) compared to the inhaled corticosteroids (> 5 × 10{sup −6} cm/s), except for budesonide, with permeability similar to the systemic corticosteroids. Inhaled corticosteroids are not transported by P-gp to the same extent as systemic corticosteroids. However, they are able to induce P-gp production. Thus, inhaled corticosteroids may have greater interactions with other P-gp substrates, but P-gp itself is less likely to influence resistance to the drugs. -- Highlights: ► Inhaled corticosteroids are only weak substrates for P-gp, including budesonide. ► Inhaled corticosteroid potent P-gp inducers especially

  4. Inhalant abuse by adolescents: A new challenge for Indian physicians

    Directory of Open Access Journals (Sweden)

    Basu Debasish


    Full Text Available Inhalant abuse has been commonly reported especially in the young during the last decades globally. The reason for the relative paucity of literature from India may be attributed to a lack of knowledge about this growing problem among health professionals. A series of five cases of inhalant abuse is described in order to understand this growing public health concern. Most of the cases started inhalant abuse during adolescence. All patients except one abused typewriter erasing fluid and thinner which contains toluene. All the patients reported using inhalants as addictive substance because of their easy accessibility, cheap price, their faster onset of action and the regular ′high′ that it provided. Whereas several features of inhalant dependence were fulfilled, no physical withdrawal signs were observed. The diagnosis of inhalant abuse can be difficult and relies almost entirely on clinical judgment. Treatment is generally supportive.

  5. Risks of pneumonia in patients with asthma taking inhaled corticosteroids

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Soren; Carlsson, Lars-Göran


    Rationale: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment. Studies in chronic obstructive pulmonary disease reported increased rates of pneumonia with ICS. Concerns exist about an increased pneumonia risk in patients with asthma taking ICS. Objectives: To evaluate the risks...... of pneumonia in patients with asthma taking ICS. Methods: A retrospective analysis evaluated studies of the ICS budesonide in asthma. The primary data set were all double-blind, placebo-controlled trials lasting at least 3 months, involving budesonide (26 trials, n = 9,067 for budesonide; n = 5...... effect of ICS on pneumonia adverse events (AEs) or serious adverse events (SAEs). Measurements and Main Results: In the primary data set, the occurrence of pneumonia AEs was 0.5% (rate 10.0 events/1,000 patient-years [TPY]) for budesonide and 1.2% (19.3 per TPY) for placebo (hazard ratio, 0.52; 95...

  6. Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers. (United States)

    Buttini, Francesca; Miozzi, Michele; Balducci, Anna Giulia; Royall, Paul G; Brambilla, Gaetano; Colombo, Paolo; Bettini, Ruggero; Forbes, Ben


    Solution composition alters the dynamics of beclomethasone diproprionate (BDP) particle formation from droplets emitted by pressurised metered dose inhalers (pMDIs). The hypothesis that differences in inhaler solutions result in different solid particle physical chemistry was tested using a suite of complementary calorimetric techniques. The atomisation of BDP-ethanol solutions from commercial HFA-pMDI produced aerodynamically-equivalent solid particle aerosols. However, differences in particle physico-chemistry (morphology and solvate/clathrate formation) were detected by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and supported by hot stage microscopy (HSM). Increasing the ethanol content of the formulation from 8 to 12% (w/w), which retards the evaporation of propellant and slows the increase in droplet surface viscosity, enhanced the likelihood of particles drying with a smooth surface. The dissolution rate of BDP from the 12% (w/w) ethanol formulation-derived particles (63% dissolved over 120 min) was reduced compared to the 8% (w/w) ethanol formulation-derived particles (86% dissolved over 120 min). The addition of 0.01% (w/w) formoterol fumarate or 1.3% (w/w) glycerol to the inhaler solution modified the particles and reduced the BDP dissolution rate further to 34% and 16% dissolved in 120 min, respectively. These data provide evidence that therapeutic aerosols from apparently similar inhaler products, including those with similar aerodynamic performance, may behave non-equivalently after deposition in the lungs.

  7. Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs

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    Jana Dumkova


    Full Text Available The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.

  8. Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks. (United States)

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


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

  9. Inhaled Surfactant in the treatment of accidental Talc Powder inhalation: a new case report

    Directory of Open Access Journals (Sweden)

    Lo Piparo Caterina


    Full Text Available Abstract The use of talcum powder is incorrectly part of the traditional care of infants. Its acute aspiration is a very dangerous condition in childhood. Although the use of baby powder has been discouraged from many authors and the reports of its accidental inhalation have been ever more rare, sometimes new cases with several fatalities have been reported. We report on a patient in which accidental inhalation of baby powder induced severe respiratory difficulties. We also point out the benefits of surfactant administration. Surfactant contributed to the rapid improvement of the medical and radiological condition, preventing severe early and late complications and avoiding invasive approaches.

  10. Induction of Food Allergy in Mice by Allergen Inhalation (United States)


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

  11. 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

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    Leiva-Fernández Francisca


    Full Text Available Abstract 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

  12. Influence of Natural Lung Surfactant Inhalations on Clinical Symptoms and Pulmonary Function Parameters in Patients with Bronchial Asthma. Communication 1

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    O.V. Stepanova


    Full Text Available Background: Damage to lung surfactant (LS enabling the lung local immunity may contribute to the development of bronchial inflammation in patients with bronchial asthma. Methods and Results: A 40-day course of 16 LS (Surfactant-BL inhalations at the dose of 25mg was added to inhaled corticosteroids (ICS and short/long-acting bronchodilators or combined inhalers in 14 patients with bronchial asthma. After 7 inhalations, patients demonstrated a significant decrease in shortness of breath and bronchospasm attacks, double reduction of ICS dose (p=0.01, and improvement of pulmonary function. Forced vital capacity (FVC increases during treatment in a linear fashion (y=62.9+5.60•x; p<0.05, reaching the normal level (80% after 9 inhalations (Day 15. Forced expiratory volume (FEV1 increases in a linear fashion (y=50.7+4.15•x; p<0.05 without reaching the normal level (80% after 16 inhalations (Day 41. The FEV1/FVC ratio does not change significantly in the time period between Day 1 to Day 15. By Day 41 the value decreases significantly to 67.4±4.66% (p<0.05. The peak expiratory flow (PEF parameter increases in a linear fashion (y=53.9+5.00•x; p<0.01 from 57.7±6.33% to 76.2±9.33% of the predicted value. Conclusion: LS inhalations improve the condition of patients with BA, allow ICS dose reduction by 2 times, and improve pulmonary function parameters.

  13. Terbutaline accumulates in blood and urine following daily therapeutic inhalation

    DEFF Research Database (Denmark)

    Krogh, Nanna; Rzeppa, Sebastian; Dyreborg, Anders


    ×d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high...... consecutive days of inhalation. For doping control purposes, these observations are of relevance if a urine threshold and decision limit is to be introduced for terbutaline on the World Anti-Doping Agency's list of prohibited substances, since asthmatic athletes may use their bronchorelievers for consecutive...

  14. Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat® Soft Mist™ Inhaler

    Directory of Open Access Journals (Sweden)

    Richard Hodder


    Full Text Available Richard Hodder,1 David Price21Divisions of Pulmonary and Critical Care, University of Ottawa, Ottawa, Ontario, Canada; 2Department of General Practice and Primary Care, University of Aberdeen, Aberdeen, ScotlandAbstract: Current guidelines for the management of chronic obstructive pulmonary disease (COPD recommend the regular use of inhaled bronchodilator therapy in order to relieve symptoms and prevent exacerbations. A variety of inhaler devices are currently available to COPD patients, and the choice of device is an important consideration because it can influence patients’ adherence to treatment, and thus potentially affect the long-term outcome. The Respimat® Soft Mist™ Inhaler (SMI generates a slow-moving aerosol with a high fine particle fraction, resulting in deposition of a higher proportion of the dose in the lungs than pressurized metered-dose inhalers (pMDIs or some dry powder inhalers (DPIs. We review clinical studies of inhaler satisfaction and preference comparing Respimat® SMI against other inhalers in COPD patients. Using objective and validated patient satisfaction instruments, Respimat® SMI was consistently shown to be well accepted by COPD patients, largely due to its inhalation and handling characteristics. In comparative studies with pMDIs, the patient total satisfaction score with Respimat® SMI was statistically and clinically significantly higher than with the pMDI. In comparative studies with DPIs, the total satisfaction score was statistically significantly higher than for the Turbuhaler® DPI, but only the performance domain of satisfaction was clinically significantly higher for Respimat® SMI. Whether the observed higher levels of patient satisfaction reported with Respimat® SMI might be expected to result in improved adherence to therapy and thus provide benefits consistent with those recently shown to be associated with sustained bronchodilator treatment in patients with COPD remains to be proven

  15. Tolerability of inhaled N-chlorotaurine in the pig model

    Directory of Open Access Journals (Sweden)

    Scholl-Bürgi Sabine


    Full Text Available Abstract Background N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT in the pig model. Methods Anesthetized pigs inhaled test solutions of 1% (55 mM NCT (n = 7, 5% NCT (n = 6, or 1% NCT plus 1% ammonium chloride (NH4Cl (n = 6, and 0.9% saline solution as a control (n = 7, respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed. Results Arterial pressure of oxygen (PaO2 decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014 with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2 (p = 0.004. Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016. The increase of pulmonary artery pressure (PAP over the observation period was smallest with 1% NCT without difference to controls (p = 0.91, and higher with 5% NCT (p = 0.02, and NCT + NH4Cl (p = 0.05. Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25–0.5 mM. Conclusion The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of

  16. National trends in burn and inhalation injury in burn patients: results of analysis of the nationwide inpatient sample database. (United States)

    Veeravagu, Anand; Yoon, Byung C; Jiang, Bowen; Carvalho, Carla M; Rincon, Fred; Maltenfort, Mitchell; Jallo, Jack; Ratliff, John K


    The aim of this study was describe national trends in prevalence, demographics, hospital length of stay (LOS), hospital charges, and mortality for burn patients with and without inhalational injury and to compare to the National Burn Repository. Burns and inhalation injury cause considerable mortality and morbidity in the United States. There remains insufficient reporting of the demographics and outcomes surrounding such injuries. The National Inpatient Sample database, the nation's largest all-payer inpatient care data repository, was utilized to select 506,628 admissions for burns from 1988 to 2008 based on ICD-9-CM recording. The data were stratified based on the extent of injury (%TBSA) and presence or absence of inhalational injury. Inhalation injury was observed in only 2.2% of burns with burns with 80 to 99% TBSA. Burn patients with inhalation injury were more likely to expire in-hospital compared to those without (odds ratio, 3.6; 95% confidence interval, 2.7-5.0; P Patients treated at rural facilities and patients with hyperglycemia had lower mortality rates. Each increase in percent of TBSA of burns increased LOS by 2.5%. Patients with burns covering 50 to 59% of TBSA had the longest hospital stay at a median of 24 days (range, 17-55). The median in-hospital charge for a burn patient with inhalation injury was US$32,070, compared to US$17,600 for those without. Overall, patients who expired from burn injury accrued higher in-hospital charges (median, US$50,690 vs US$17,510). Geographically, California and New Jersey were the states with the highest charges, whereas Vermont and Maryland were states with the lowest charges. The study analysis provides a broad sampling of nationwide demographics, LOS, and in-hospital charges for patients with burns and inhalation injury.

  17. Tobramycin Inhalation Powder (TIP): An Efficient Treatment Strategy for the Management of Chronic Pseudomonas Aeruginosa Infection in Cystic Fibrosis. (United States)

    Lam, John; Vaughan, Steven; Parkins, Michael D


    Repeated bouts of acute and chronic lung infections are responsible for progressive pulmonary function decline in individuals with cystic fibrosis (CF), ultimately leading to respiratory failure and death. Pseudomonas aeruginosa is the archetypical CF pathogen, causes chronic infection in 70% of individuals, and is associated with an accelerated clinical decline. The management of P. aeruginosa in CF has been revolutionized with the development and widespread use of inhaled antibiotics. Aerosol delivery of antimicrobial compounds in CF enables extremely high concentrations of antibiotics to be reached directly at the site of infection potentially overcoming adaptive resistance and avoiding the potential for cumulative systemic toxicities. Tobramycin inhalation powder (TIP) represents the first dry powder inhaled (DPI) antibiotic available for use in CF. DPIs are notable for a markedly reduced time for administration, ease of portability, and increased compliance. TIP has been developed as a therapeutic alternative to tobramycin inhalation solution (TIS), the standard of care for the past 20 years within CF. Relative to TIS 300 mg nebulized twice daily in on-and-off cycles of 28 days duration, TIP 112 mg twice daily via the T-326 inhaler administered on the same schedule is associated with marked time savings, increased patient satisfaction, and comparable clinical end points. TIP represents an innovative treatment strategy for those individuals with CF and holds the promise of increased patient compliance and thus the potential for improved clinical outcomes.

  18. Nanospray Drying as a Novel Technique for the Manufacturing of Inhalable NSAID Powders

    Directory of Open Access Journals (Sweden)

    Aquino Rita Patrizia


    Full Text Available The aim of this research was to evaluate the potential of the nanospray drier as a novel apparatus for the manufacturing of a dry powder for inhalation containing ketoprofen lysinate, a nonsteroidal anti-inflammatory drug able to control the inflammation in cystic fibrosis patients. We produced several ketoprofen lysinate and leucine powder batches by means of nanospray dryer, studying the influence of process parameters on yield, particle properties (size distribution and morphology, and, mainly, aerodynamic properties of powders. Micronized particles were prepared from different hydroalcoholic solutions (alcohol content from 0 to 30% v/v using ketoprofen in its lysine salt form and leucine as dispersibility enhancer in different ratios (from 5 to 15% w/w with a total solid concentration ranging from 1 to 7% w/v. Results indicated that the spray head equipped with a 7 µm nozzle produced powders too big to be inhaled. The reduction of nozzle size from 7 to 4 µm led to smaller particles suitable for inhalation but, at the same time, caused a dramatic increase in process time. The selection of process variables, together with the nozzle pretreatment with a surfactant solution, allowed us to obtain a free flowing powder with satisfying aerosol performance, confirming the usefulness of the nanospray drier in the production of powder for inhalation.

  19. Therapeutic effect of glucocorticoid inhalation for pulmonary fibrosis in ARDS patients

    Directory of Open Access Journals (Sweden)

    Wen-biao ZHAO


    Full Text Available Objective To observe the effect of glucocorticoid inhalation on the clinical symptoms and pulmonary fibrosis index in ARDS patients. Methods Fifty-three ARDS patients admitted to ICU of Songjiang District Center Hospital of Shanghai from Dec. 2011 to Jun. 2013 were randomly divided into two groups. Group A (n=29 received conventional therapy, and group B (n=24 was given glucocorticoid inhalation treatment (budesonide, 2 mg, 1/12 h, for 12 days on the basis of the conventional therapy. The oxygenation index, time of extubation, changes in pulmonary fibrosis index, including collagen Ⅰ(Co Ⅰ, Ⅲ procollagen peptide (PⅢP and transforming growth factor (TGF-β1 were compared between the two groups, and the incidence of common adverse reactions were analyzed. Results The oxygenation index of patients in group B was significantly improved on the 15th day compared with group A (P0.05. Conclusion A small dose of glucocorticoids introduced by inhalation can improve the oxygenation index and pulmonary fibrosis level without increasing common adverse reactions, suggesting that the inhalation of corticosteroid may be a clinically safe and effective way in patients with ARDS. DOI: 10.11855/j.issn.0577-7402.2014.09.13

  20. 45. Damage effects of sulfur dioxide inhalation on DNA of brain cells from mice

    Institute of Scientific and Technical Information of China (English)


    The damage effects of sulfur dioxide (SO2) inhalation on DNA of brain cells from mice were studied with the single cell microgel electrophoresis tecknique (Comet test). The results show that SO2 inhalation caused the damage effects to DNA of the mouse brain cells in a dose-dependent manner. The results indicate that even under SO2 inhalation at low concentrations as 7 mg SO2/m3, The brain cells with DNA damaged also reached to 98.8%, it implies the brain cells of mammalian animals are very sensitive to SO2 inhalation. The results also indicate that DNA damage of the brain cells from male mice is more serious than that from female mice, that remains to be further studied. These results led us to conclusion SO2 pollution even at low concentrations also has a potential risk to damage genetic material DNA of brain cells from mammalian animals. It might be explained by our conclusion that the recently published epidemiological studies of workers exposed to SO2 or it's derivatives (bi)sulfite) found increased mortality for brain cancer.

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

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


    This study focused on the generation of aerosols of titanium dioxide (TiO2) nanoparticles (NPs) and their disposition kinetics in rats. Male Sprague-Dawley rats were exposed by inhalation to 15mg/m(3) of anatase TiO2 NPs (∼20nm) during 6h. Rats were sacrificed at different time points over 14days following the onset of inhalation. Ti levels were quantified by ICP-MS in blood, tissues, and excreta. Oxidative damages were also monitored (MDA). Highest tissue levels of Ti were found in lungs; peak values were reached only at 48h followed by a progressive decrease over 14days, suggesting a persistence of NPs at the site-of-entry. Levels reached in blood, lymph nodes and other internal organs (including liver, kidney, spleen) were circa one order of magnitude lower than in lungs, but the profiles were indicative of a certain translocation to the systemic circulation. Large amounts were recovered in feces compared to urine, suggesting that inhaled NPs were eliminated mainly by mucociliary clearance and ingested. TiO2 NPs also appeared to be partly transferred to olfactory bulbs and brain. MDA levels indicative of oxidative damage were significantly increased in lungs and blood at 24h but this was not clearly reflected at later times. Translocation and clearance rates of inhaled NPs under different realistic exposure conditions should be further documented.

  2. Low flow and economics of inhalational anaesthesia. (United States)

    Odin, I; Feiss, P


    Even when anaesthesia does not represent a major part of the expense of a given surgical operation, reducing costs is not negligible because the large number of patients passing through a department of anaesthesia accounts for a huge annual budget. Volatile anaesthetics contribute 20% of the drug expenses in anaesthesia, coming just behind the myorelaxants; however, the cost of halogenated agents has potential for savings because a significant part of the delivered amount is wasted when a non- or partial-rebreathing system is used. The cost of inhaled agents is related to more than the amount taken up; it also depends on their market prices, their relative potencies, the amount of vapour released per millilitre of liquid, and last but not least the fresh-gas flow rate (FGF) delivered to the vaporizer--the most important factor determining the cost of anaesthesia. Poorly soluble agents like desflurane and sevoflurane facilitate the control of low-flow anaesthesia and reduce the duration of temporary high-flow phases to rapidly wash in or adjust the circuit gas concentrations. Modelling low-flow or minimal-flow anaesthesia will help anaesthetists to understand the kinetics of inhaled agents in those circumstances and to design their own clinical protocols. The monitoring facilities present on modern anaesthesia machines should convince clinicians that low- or even minimal-flow anaesthesia would not jeopardize the safety of their patients. Cost containment requires primarily a decrease in FGFs, but it may also be influenced by a rational use of the available halogenated agents. Isoflurane, the cheapest generic agent, might be advantageous for maintenance of anaesthesia of less than 3 hours. Sevoflurane is the agent of choice for inhalational induction and might also be used for maintenance. Desflurane might be preferred for long anaesthetics where rapid recovery will generate savings in the PACU.

  3. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)


    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  4. Inhalable DNase I microparticles engineered with biologically active excipients. (United States)

    Osman, Rihab; Al Jamal, Khuloud T; Kan, Pei-Lee; Awad, Gehanne; Mortada, Nahed; El-Shamy, Abd-Elhameed; Alpar, Oya


    Highly viscous mucus poses a big challenge for the delivery of particulates carrying therapeutics to patients with cystic fibrosis. In this study, surface modifying DNase I loaded particles using different excipients to achieve better lung deposition, higher enzyme stability or better biological activity had been exploited. For the purpose, controlled release microparticles (MP) were prepared by co-spray drying DNase I with the polymer poly-lactic-co-glycolic acid (PLGA) and the biocompatible lipid surfactant 1,2-dipalmitoyl-Sn-phosphatidyl choline (DPPC) using various hydrophilic excipients. The effect of the included modifiers on the particle morphology, size, zeta potential as well as enzyme encapsulation efficiency, biological activity and release had been evaluated. Powder aerosolisation performance and particle phagocytosis by murine macrophages were also investigated. The results showed that more than 80% of enzyme activity was recovered after MP preparation and that selected surface modifiers greatly increased the enzyme encapsulation efficiency. The particle morphology was greatly modified altering in turn the powders inhalation indices where dextran, ovalbumin and chitosan hydrochloride increased considerably the respirable fraction compared to the normal hydrophilic carriers lactose and PVP. Despite of the improved aerosolisation caused by chitosan hydrochloride, yet retardation of chitosan coated particles in artificial mucus samples discouraged its application. On the other hand, dextran and polyanions enhanced DNase I effect in reducing cystic fibrosis mucus viscosity. DPPC proved good ability to reduce particles phagocytic uptake even in the presence of the selected adjuvants. The prepared MP systems were biocompatible with lung epithelial cells. To conclude, controlled release DNase I loaded PLGA-MP with high inhalation indices and enhanced mucolytic activity on CF sputum could be obtained by surface modifying the particles with PGA or dextran.

  5. Inhaled analgesia for pain management in labour (Review)

    NARCIS (Netherlands)

    Klomp, T.; Poppel, M. van; Jones, L.; Lazet, J.; Nisio, M. Di; Lagro-Janssen, A.L.M.


    BACKGROUND: Many women would like to have a choice in pain relief during labour and also would like to avoid invasive methods of pain management in labour. Inhaled analgesia during labour involves the self-administered inhalation of sub-anaesthetic concentrations of agents while the mother remains a

  6. Urine and serum concentrations of inhaled and oral terbutaline

    DEFF Research Database (Denmark)

    Elers, Jimmi; Hostrup, Morten; Pedersen, Lars


    We examined urine and serum concentrations after therapeutic use of single and repetitive doses of inhaled and supratherapeutic oral use of terbutaline. We compared the concentrations in 10 asthmatics and 10 healthy subjects in an open-label, cross-over study with 2 mg inhaled and 10 mg oral terb...... therapeutic and prohibited use based on doping tests with urine and blood samples....

  7. Conceptual model for assessment of inhalation exposure: Defining modifying factors

    NARCIS (Netherlands)

    Tielemans, E.; Schneider, T.; Goede, H.; Tischer, M.; Warren, N.; Kromhout, H.; Tongeren, M. van; Hemmen, J. van; Cherrie, J.W.


    The present paper proposes a source-receptor model to schematically describe inhalation exposure to help understand the complex processes leading to inhalation of hazardous substances. The model considers a stepwise transfer of a contaminant from the source to the receptor. The conceptual model is c

  8. A review of inhalability fraction models: discussion and recommendations. (United States)

    Millage, Kyle K; Bergman, Josh; Asgharian, Bahman; McClellan, Gene


    The first step in mathematically modeling the mechanics of respiratory deposition of particles is to estimate the ability of a particle to enter the head, either through the mouth or nose. Models of the biological effects from inhaled particles are commonly, albeit incorrectly, simplified by making an assumption that the only particles of concern are those that can readily penetrate to the pulmonary region of the lung: typically particles less than 5microm in aerodynamic diameter. Inhalability for particles of this size is effectively 100%, so there is little need to develop a mathematical representation of the phenomenon. However, chemical irritants, biological agents, or radioactive material, in the form of large particles or droplets, can cause adverse biological responses by simply being taken into the head and depositing in the extrathoracic area. As a result, it is important to understand the inhalability of both small and large particles. The concept of particle inhalability received little consideration until the 1970s; since then it has been the subject of many experiments with a fairly wide disparity of results, in part due to the variety of dependent variables and the difficulty in adequate measurement methods. This article describes the currently utilized models of inhalability, recommends specific methods for implementing inhalability into mathematical models of respiratory deposition, and identifies outstanding issues and limitations. In this article, we describe inhalability as it applies to particulate matter and liquid droplets; modeling the inhalability of fibers is a work in progress and is not addressed.

  9. Technological and practical challenges of dry powder inhalers and formulations

    NARCIS (Netherlands)

    Hoppentocht, M.; Hagedoorn, P.; Frijlink, H.W.; de Boer, A.H.


    In the 50 years following the introduction of the first dry powder inhaler to the market, several developments have occurred. Multiple-unit dose and multi-dose devices have been introduced, but first generation capsule inhalers are still widely used for new formulations. Many new particle engineerin

  10. Carbon monoxide inhalation ameliorates conditions of lung grafts from rat brain death donors

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hua-cheng; DING Wen-gang; CUI Xiao-guang; PAN Peng; ZHANG Bing; LI Wen-zhi


    Background Successful lung transplantation has been limited by the scarcity of donors. Brain death (BD) donors are major source of lung transplantation. Whereas BD process induces acute lung injury and aggravates lung ischemia reperfusion injury. Carbon monoxide (CO) inhalation at 50-500 parts per million (ppm) can ameliorate lung injury in several models. We examined in rats whether CO inhalation in BD donor would show favorable effects on lung grafts.Methods Rats were randomly divided into 4 groups. In sham group, donor rats received insertion of a balloon catheter into the cranial cavity, but the balloon was not inflated. In BD-only group, donor rats were ventilated with 40% oxygen after BD confirmation. In BD+CO250 and BD+CO500 groups, donor rats inhaled, after BD confirmation, 250 ppm or 500 ppm CO for 120 minutes prior to lung procurement, and orthotopic lung transplantation was performed. The rats were sacrificed 120 minutes after the lung transplantation by exsanguination, and their blood and lung graft samples were obtained. A total of 8 rats fulfilling the criteria were included in each group.Results The inhalation decreased the severity of lung injury in grafts from BD donors checked by histological examination. CO pretreatment reversed the aggravation of PaO2/FiO2 in recipients from BD donors. The CO inhalation down-regulated pro-inflammatory cytokines (TNF-α, IL-6) along with the increase of anti-inflammatory cytokine (IL-10) in recipient serum, and inhibited the activity of myeloperoxidase in grafts tissue. The inhalation significantly decreased cell apoptosis in lung grafts, inhibiting mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and caspase-3 in lung grafts. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of anti-extraceUular signal-regulated kinase (ERK) expression in lung grafts. The effects of CO at 500 ppm were greater than those at 250 ppm.Conclusions CO exerts

  11. Design and evaluation of a new dry powder inhaler

    Directory of Open Access Journals (Sweden)

    "Rouholamini Najafabadi AH


    Full Text Available Three versions of a new dry powder inhaler (DPI, RG-haler, were designed using two kinds of grid inserts. Salbutamol sulfate/lactose blend (Ventolin Rotacaps® was selected as a model formulation to analyze the performance of all inhalers and compare their efficiency with three marketed devices (Rotahaler®, Spinhaler® and ISF inhalator® using the twin impinger (TI. Deposition of the drug in device was significantly (P<0.05 lower for ISF inhalator® and all kinds of RG-halers in comparison with those of Rotahaler® and Spinhaler®. The amount of drug deposited in the stage 2 and the respirable dose for RG-halers were similar to those of ISF inhalator® and significantly (P<0.05 higher than those of Rotahaler® and Spinhaler®. The results suggest efficient aerosol generating capability of the RG-haler.

  12. Abused inhalants and central reward pathways: electrophysiological and behavioral studies in the rat. (United States)

    Riegel, Arthur C; French, Edward D


    Inhalant abuse remains a significant health problem among the younger segment of society. In fact, the use of inhalants in this population trails only that of nicotine, alcohol, and marijuana. Toluene is a common ingredient in many of the substances sought out for inhalation abuse, apparently for its euphorigenic and hallucinogenic effects. Because drugs of abuse share the common property of altering the activity of mesolimbic dopamine neurons, it is reasonable to suspect that toluene-induced changes in this CNS pathway may underlie its abuse potential. Here we will provide in vivo and in vitro electrophysiological data and behavioral evidence linking toluene exposure in rats to activation of mesolimbic dopamine neurons. Exposure of rats to 11,000 ppm of inhaled toluene produced time-dependent activation of dopamine neurons within the midbrain ventral tegmental area (VTA). In the rat brain slice preparation, perfusion with toluene (23-822 microM) also evoked an increase in activity of both dopamine and nondopamine neurons within the VTA. These excitatory effects could not be found in adjacent non-VTA nuclei, nor were they sensitive to the glutamate antagonists CGS19755 or CNQX. In behavioral studies, systemic administration of toluene produced a dose-dependent locomotor hyperactivity that was attenuated by either pretreatment with the D2 dopamine receptor antagonist remoxipride or by 6-hydroxydopamine lesions of the nucleus accumbens. These findings show that toluene can activate dopamine neurons within the mesolimbic reward pathway, an effect that may underlie the abuse potential of inhaled substances containing toluene.

  13. Personal exposure to inhalable cement dust among construction workers. (United States)

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


    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.

  14. Syringe, pen, inhaler - the evolution of insulin therapy. (United States)

    Harsch, I A; Hahn, E G; Konturek, P C


    The therapy with inhalable insulin can be expected to change the present concepts and the market of subcutaneous insulin dramatically within the next years. Several companies are currently developing formulations of inhalable insulin. In the most advanced concept, insulin is delivered as a dry-powder insulin formulation via a special aerosol device system. The phase III studies evaluating the efficiency of the inhaled insulin are already on their way. The recent phase II studies have shown, that the lung is capable of absorbing new insulin formulation in a dose-dependent and reproducible manner. However, a relatively small number of diabetic patients have been included in these studies, yet. The therapeutic efficacy and safety of the inhaled insulin is comparable to that of the usual subcutaneous insulin treatment regimens. The most important advantage of the new therapy is the enhanced therapeutic comfort of the patient who does not need to inject insulin for meal time glucose control. Generally, in terms of glycemic control, inhalable insulin offers no advantages in type 1 diabetics in comparison to an intensified conventional insulin therapy. However, before a large-scale marketing, several open questions have to be carefully investigated, the most important being the possible long-term effects of insulin inhalation for the lung, since insulin is known to have growth-promoting properties. There is still no available clinical data concerning the efficiency of the inhaled insulin in patients with pulmonary diseases which may cause problems in absorption of inhaled insulin due to the smaller cumulative alveolar surface. In smokers without pulmonary disease seems the inhaled insulin to act stronger and faster. Since therapy with inhalable insulin requires larger doses of insulin in comparison to subcutaneous insulin to achieve the same systemic effect, the costs of this therapy need to be clarified, too.

  15. Toxicologic evaluation of tungsten: 28-day inhalation study of tungsten blue oxide in rats. (United States)

    Rajendran, Narayanan; Hu, Shu-Chieh; Sullivan, Dennis; Muzzio, Miguel; Detrisac, Carol J; Venezia, Carmen


    The toxicity and toxicokinetics of tungsten blue oxide (TBO) were examined. TBO is an intermediate in the production of tungsten powder, and has shown the potential to cause cellular damage in in vitro studies. However, in vivo evidence seems to indicate a lack of adverse effects. The present study was undertaken to address the dearth of longer-term inhalation toxicity studies of tungsten oxides by investigating the biological responses induced by TBO when administered via nose-only inhalation to rats at levels of 0.08, 0.325, and 0.65 mg TBO/L of air for 6 h/day for 28 consecutive days, followed by a 14-day recovery period. Inhaled TBO was absorbed systemically and blood levels of tungsten increased as inhaled concentration increased. Among the tissues analyzed for tungsten levels, lung, femur and kidney showed increased levels, with lung at least an order of magnitude greater than kidney or femur. By exposure day 14, tungsten concentration in tissues had reached steady-state. Increased lung weight was noted for both terminal and recovery animals and was attributed to deposition of TBO in the lungs, inducing a macrophage influx. Microscopic evaluation of tissues revealed a dose-related increase in alveolar pigmented macrophages, alveolar foreign material and individual alveolar foamy macrophages in lung. After a recovery period there was a slight reduction in the incidence and severity of histopathological findings. Based on the absence of other adverse effects, the increased lung weights and the microscopic findings were interpreted as nonadverse response to exposure and were not considered a specific reaction to TBO.

  16. Generation and Characterization of Indoor Fungal Aerosols for Inhalation Studies. (United States)

    Madsen, Anne Mette; Larsen, Søren T; Koponen, Ismo K; Kling, Kirsten I; Barooni, Afnan; Karottki, Dorina Gabriela; Tendal, Kira; Wolkoff, Peder


    In the indoor environment, people are exposed to several fungal species. Evident dampness is associated with increased respiratory symptoms. To examine the immune responses associated with fungal exposure, mice are often exposed to a single species grown on an agar medium. The aim of this study was to develop an inhalation exposure system to be able to examine responses in mice exposed to mixed fungal species aerosolized from fungus-infested building materials. Indoor airborne fungi were sampled and cultivated on gypsum boards. Aerosols were characterized and compared with aerosols in homes. Aerosols containing 10(7)CFU of fungi/m(3)air were generated repeatedly from fungus-infested gypsum boards in a mouse exposure chamber. Aerosols contained Aspergillus nidulans,Aspergillus niger, Aspergillus ustus, Aspergillus versicolor,Chaetomium globosum,Cladosporium herbarum,Penicillium brevicompactum,Penicillium camemberti,Penicillium chrysogenum,Penicillium commune,Penicillium glabrum,Penicillium olsonii,Penicillium rugulosum,Stachybotrys chartarum, and Wallemia sebi They were all among the most abundant airborne species identified in 28 homes. Nine species from gypsum boards and 11 species in the homes are associated with water damage. Most fungi were present as single spores, but chains and clusters of different species and fragments were also present. The variation in exposure level during the 60 min of aerosol generation was similar to the variation measured in homes. Through aerosolization of fungi from the indoor environment, cultured on gypsum boards, it was possible to generate realistic aerosols in terms of species composition, concentration, and particle sizes. The inhalation-exposure system can be used to study responses to indoor fungi associated with water damage and the importance of fungal species composition.

  17. The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study. (United States)

    Eisenberg, Elon; Ogintz, Miri; Almog, Shlomo


    Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC₀→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.

  18. Risk of Pneumonia with Inhaled Corticosteroid versus Long-Acting Bronchodilator Regimens in Chronic Obstructive Pulmonary Disease: A New-User Cohort Study


    DiSantostefano, Rachael L; Tim Sampson; Hoa Le; David Hinds; Davis, Kourtney J; Nawar Diar Bakerly


    INTRODUCTION: Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. OBJECTIVE: To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. ...

  19. Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury. (United States)

    Maile, Robert; Jones, Samuel; Pan, Yinghao; Zhou, Haibo; Jaspers, Ilona; Peden, David B; Cairns, Bruce A; Noah, Terry L


    Bacterial infection is a major cause of morbidity affecting outcome following burn and inhalation injury. While experimental burn and inhalation injury animal models have suggested that mediators of cell damage and inflammation increase the risk of infection, few studies have been done on humans. This is a prospective, observational study of patients admitted to the North Carolina Jaycee Burn Center at the University of North Carolina who were intubated and on mechanical ventilation for treatment of burn and inhalational injury. Subjects were enrolled over a 2-yr period and followed till discharge or death. Serial bronchial washings from clinically indicated bronchoscopies were collected and analyzed for markers of tissue injury and inflammation. These include damage-associated molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1 (HMGB-1). The study population was comprised of 72 patients who had bacterial cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels in bronchial washings obtained early (the first 72 h after injury) were significantly associated with positive bacterial respiratory cultures obtained during the first 14 days postinjury. Independent of initial inhalation injury severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the central airways obtained early after injury are associated with subsequent positive bacterial respiratory cultures in patients intubated after acute burn/inhalation injury.

  20. Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice (United States)

    Etani, Reo; Kataoka, Takahiro; Kanzaki, Norie; Sakoda, Akihiro; Tanaka, Hiroshi; Ishimori, Yuu; Mitsunobu, Fumihiro; Yamaoka, Kiyonori


    Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)–induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. PMID:27021217

  1. Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

    Directory of Open Access Journals (Sweden)

    Ratzan Susan


    Full Text Available Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually limited to biochemical abnormalities, with no obvious clinical effects. Acute adrenal crisis is much rarer event but has been reported with increasing frequency. We report a case of a 7-year-old asthmatic child who presented with an acute history of lethargy after a respiratory infection. He was maintained on 220 g/day of fluticasone propionate for several years. Initial evaluation revealed severe adrenal suppression, with undetectable cortisol levels and minimal response after stimulation with ACTH. After fluticasone was discontinued, a gradual recovery of the adrenal axis was seen. This case shows that acute adrenal crisis may be a consequence even at the usual prescribed doses, stressing the importance of using the lowest dose of inhaled steroids needed to control symptoms and having an increased awareness of this complication.

  2. Acute Adrenal Crisis in an Asthmatic Child Treated with Inhaled Fluticasone Proprionate

    Directory of Open Access Journals (Sweden)

    Angela H. Santiago


    Full Text Available Adrenal suppression secondary to prolonged inhaled corticosteroid use is usually limited to biochemical abnormalities, with no obvious clinical effects. Acute adrenal crisis is much rarer event but has been reported with increasing frequency. We report a case of a 7-year-old asthmatic child who presented with an acute history of lethargy after a respiratory infection. He was maintained on 220 μg/day of fluticasone propionate for several years. Initial evaluation revealed severe adrenal suppression, with undetectable cortisol levels and minimal response after stimulation with ACTH. After fluticasone was discontinued, a gradual recovery of the adrenal axis was seen. This case shows that acute adrenal crisis may be a consequence even at the usual prescribed doses, stressing the importance of using the lowest dose of inhaled steroids needed to control symptoms and having an increased awareness of this complication.

  3. Hepatotumorigenicity of ethyl tertiary-butyl ether with 2-year inhalation exposure in F344 rats. (United States)

    Saito, Arata; Sasaki, Toshiaki; Kasai, Tatuya; Katagiri, Taku; Nishizawa, Tomoshi; Noguchi, Tadashi; Aiso, Shigetoshi; Nagano, Kasuke; Fukushima, Shoji


    Carcinogenicity of ethyl tertiary-butyl ether (ETBE) was examined with inhalation exposure using F344/DuCrlCrlj rats. Groups of 50 male and 50 female rats, 6 week old at commencement, were exposed to ETBE at 0, 500, 1,500 or 5,000 ppm (v/v) in whole-body inhalation chambers for 6 h/day, 5 days/week for 104 weeks. A significant increase in the incidence of hepatocellular adenomas was indicated in males exposed at 5,000 ppm, but not in females at any concentration. In addition, significantly increased incidences of eosinophilic and basophilic cell foci were observed in male rats at 5,000 ppm. Regarding non-neoplastic lesions, rat-specific changes were observed in kidney, with an increase in the severity of chronic progressive nephropathy in both sexes at 5,000 ppm. Increased incidences of urothelial hyperplasia of the pelvis were observed at 1,500 ppm and above, and mineral deposition was apparent in the renal papilla at 5,000 ppm in males. There were no treatment-related histopathological changes observed in any other organs or tissues in either sex. The present 2-year inhalation study demonstrated hepatotumorigenicity of ETBE in male, but not in female rats.

  4. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.; Henkes, H.; Kuehne, D. [Klinik fuer Allgemeine Roentgendiagnostik und Neuroradiologie, Alfried-Krupp-Krankenhaus, Alfried Krupp Strasse 21, D-45117, Essen (Germany); Moeller, P.; Bade, K. [Neurologische Klinik, Knappschafts-Krankenhaus, D-45657 Recklinghausen (Germany)


    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.) With 2 figs., 2 tabs., 26 refs.

  5. Asthma and Adherence to Inhaled Corticosteroids

    DEFF Research Database (Denmark)

    Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli


    Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, ... prescribed fixed-combination therapy (ICS and long-acting β2 agonists). Good adherence was associated with higher FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations, less use of oral corticosteroids, and lower mortality rate. Overall, 24% of exacerbations and 60% of asthma...

  6. Survivor from asphyxiation due to helium inhalation

    Directory of Open Access Journals (Sweden)

    Massimiliano Etteri


    Full Text Available In this rare case report we describe a 27- year-old white man survived to suicide by asphyxiation using the so-called suicide bag (or exit bag filled with helium supplied through a plastic tube. He had no previous psychiatric or organic illnesses. At the time of presentation to our Emergency Department he was awake and reported severe dyspnea with a clinical pattern of acute respiratory failure. Imaging studies showed pulmonary edema and the patient was treated with non-invasive ventilation in Intensive Care Unit. After 15 days the patient was discharged from hospital in optimal conditions. These rare cases of survivor might suggest the possible causes of death from inhaling helium.

  7. [Wood dust as inhalative noxious agent]. (United States)

    Kirsten, D; Liebetrau, G; Meister, W


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

  8. Vanadium Inhalation in a Mouse Model for the Understanding of Air-Suspended Particle Systemic Repercussion

    Directory of Open Access Journals (Sweden)

    T. I. Fortoul


    Full Text Available There is an increased concern about the health effects that air-suspended particles have on human health which have been dissected in animal models. Using CD-1 mouse, we explore the effects that vanadium inhalation produce in different tissues and organs. Our findings support the systemic effects of air pollution. In this paper, we describe our findings in different organs in our conditions and contrast our results with the literature.

  9. The risk and outcomes of pneumonia in patients on inhaled corticosteroids. (United States)

    Sibila, Oriol; Soto-Gomez, Natalia; Restrepo, Marcos I


    Corticosteroids are frequently prescribed anti-inflammatory medications. Inhaled corticosteroids (ICS) are indicated for Chronic Obstructive Pulmonary Disease (COPD) and asthma. ICS are associated with a decrease in exacerbations and improved quality of life in COPD, however multiple studies have linked the chronic use of ICSs with an increased risk of developing pneumonia, though the effect on mortality is unclear. We review the association of ICS with the risk of pneumonia and the implications on clinical outcomes.

  10. Rapid transepithelial transport of prions following inhalation. (United States)

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


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

  11. Tobramycin inhalation powder: an efficient and efficacious therapy for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis. (United States)

    Somayaji, Ranjani; Parkins, Michael D


    Inhaled antipseudomonal therapies are critical components in the management of cystic fibrosis (CF) and have significantly contributed to improved patient outcomes. Dry powder inhaler technologies represent a significant advance in drug delivery, alleviating treatment burden and potentially improving adherence associated with traditional CF nebulized therapies. Tobramycin inhalation powder (TIP) uses PulmoSphere(®) technology for very efficient drug delivery into the lower airways. In placebo-controlled and comparative studies with traditional tobramycin formulations, TIP is equally efficacious and is associated with increased patient convenience and satisfaction. TIP has been recommended in the 2013 CF Foundation and the 2014 European guidelines as a therapy in CF for the maintenance of lung health. Going forward, TIP may offer a therapeutic advantage over traditional formulations of tobramycin as recent prospective 'real world' studies of TIP have demonstrated high patient tolerance and improved adherence compared with traditional formulations.

  12. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed


    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression......, consistent with SRA function in binding oxidized lipids. SR-AI/II-/- mice showed similar enhanced acute lung inflammation after beta-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II-/- versus SR-AI...

  13. The Chemo and the Mona: Inhalants, devotion and street youth in Mexico City

    NARCIS (Netherlands)

    Gigengack, R.A.


    This paper understands inhalant use – the deliberate inhalation of volatile solvents or glues with intentions of intoxication – as a socially and culturally constituted practice. It describes the inhalant use of young street people in Mexico City from their perspective (“the vicioso or inhalant fien

  14. Age of Inhalant First Time Use and Its Association to the Use of Other Drugs (United States)

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


    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…

  15. Four inhalation devices for salbutamol : in vivo and in vitro comparison in asthma and COPD

    NARCIS (Netherlands)

    Broeders, M.E.A.C.


    Inhalation therapy with bronchodilators is one of the cornerstones of the treatment of asthma and chronic obstructive pulmonary disease (COPD). Several inhalation drug-device combinations are available. Multiple factors, like the inhalation device and the inhalation technique influence the depositio

  16. Measurements and prediction of inhaled air quality with personalized ventilation

    DEFF Research Database (Denmark)

    Cermak, Radim; Majer, M.; Melikov, Arsen Krikor


    This paper examines the performance of five different air terminal devices for personalized ventilation in relation to the quality of air inhaled by a breathing thermal manikin in a climate chamber. The personalized air was supplied either isothermally or non-isothermally (6 deg.C cooler than...... the room air) at flow rates ranging from less than 5 L/s up to 23 L/s. The air quality assessment was based on temperature measurements of the inhaled air and on the portion of the personalized air inhaled. The percentage of dissatisfied with the air quality was predicted. The results suggest...

  17. Inflammogenic effect of well-characterized fullerenes in inhalation and intratracheal instillation studies

    Directory of Open Access Journals (Sweden)

    Yamamoto Kazuhiro


    Full Text Available Abstract Background We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 ± 5 nm; 0.12 ± 0.03 mg/m3; 6 hours/days for 5 days/week for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs were examined in rat lungs in both studies. Results In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2αβ and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2αβ and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2αβ and-3 in the fullerene group. Conclusion These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

  18. Size aspects of metered-dose inhaler aerosols. (United States)

    Kim, C S; Trujillo, D; Sackner, M A


    The aerodynamic size distribution of several bronchodilator and corticosteroid metered-dose inhaler (MDI) aerosols was estimated in both dry and humid (90% RH) air environments with a six-stage cascade impactor. The distribution of aerosol size that penetrated into a simulated lung model were also measured. The size distributions were approximately log-normal and ranged from 2.4 to 5.5 micron in mass median aerodynamic diameter (MMAD) with geometric standard deviation (GSD) of 1.7 to 2.5 in a dry environment. In humid air, MMAD increased from 1 to 26% above the dry air state, but GSD remained unchanged. The size of aerosol delivered by MDI that penetrated into a simulated lung model fell to 2.4 to 2.8 micron in MMAD (GSD, 1.9 to 2.2). In contrast to aerosols produced by MDI, MMAD of an aerosol of cromolyn sodium powder dispersed by a Spinhaler increased rapidly with increasing humidity, 5.6 +/- 0.3 micron in dry air and 10.1 +/- 0.8 micron in 90% RH air. Finally, the factors influencing size of MDI-delivered aerosols, including formulation, canister pressure, physicochemical properties of propellants, and design of the valve and actuator orifices are discussed. Effective delivery of MDI-generated aerosols into the lung is highly dependent on particle dynamics and jet flow, and no single parameter can produce a unique particle size and jet pattern.

  19. Cerebrovascular response to CO/sub 2/ inhalation in unanesthetized goats

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.C.; Lopez de Pablo, A.L.; Dieguez, G.; Gomez, B.; Lluch, S.


    The effects on cerebral blood flow of inhalation of 9% CO/sub 2/ in air were examined in unanesthetized goats. This procedure increased mean cerebral blood flow from 118 to 185 ml/min per 100 g and was accompanied by a rise in Pco/sub 2/ from 33 to 50 mmHg and a fall in pH from 7.41 to 7.26. Administration of phentolamine, propranolol, or atropine into the internal maxillary artery did not modify the normal cerebrovascular response to CO/sub 2/ inhalation. It is concluded that blockade of vascular adrenergic of cholinergic atropine-sensitive receptors in the goat has no effect on the cerebral vasomotor response to hypercapnia.

  20. Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure

    NARCIS (Netherlands)

    Gosens, Ilse; Cassee, Flemming R; Zanella, Michela; Manodori, Laura; Brunelli, Andrea; Costa, Anna Luisa; Bokkers, Bas G H; de Jong, Wim H; Brown, David; Hristozov, Danail; Stone, Vicki


    INTRODUCTION: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeate

  1. “My body breaks. I take solution.” Inhalant use in Delhi as pleasure seeking at a cost

    NARCIS (Netherlands)

    Gigengack, R.A.


    Background: Inhalant use has existed in India since the 1970s and has increased significantly over the last decades, especially among street-oriented young people. The latter constitute a heterogeneous category: children from street families, children 'of' the street, rag pickers, and part-time stre

  2. Inhalation of Shin-I essential oil enhances lactate clearance in treadmill exercise

    Institute of Scientific and Technical Information of China (English)

    Hsuan-Ying Chen; Ming-Fu Wang; Jun-Ying Lin; Ying-Chieh Tsai; Fu-Chou Cheng


    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.

  3. Toluene and benzene inhalation influences on ventricular arrhythmias in the rat. (United States)

    Magos, G A; Lorenzana-Jiménez, M; Vidrio, H


    We have previously found that toluene did not share the capacity of benzene for increasing the arrhythmogenic action of epinephrine in the rat, but appeared to elicit the opposite effect. The present experiments were carried out to verify this observation in rats subjected to more severe ventricular arrhythmias. In animals previously inhaling either air, toluene or benzene and anesthetized with pentobarbital, arrhythmias were produced by coronary ligation or aconitine. In both models, toluene decreased and benzene increased the number of ectopic ventricular beats in the 30 min following induction of arrhythmia. Gas chromatographic measurement of toluene levels in the heart during and after inhalation revealed essentially constant concentrations at the time of arrhythmia evaluation, equivalent to approximately one-third the peak levels observed at the end of inhalation. Although the mechanism of the effect of toluene on arrhythmia could not be ascertained, nonspecific membrane stabilization or central serotonergic stimulation were considered as possible explanations. Since both mechanisms could be operant also in the case of benzene, the opposite effects of the solvents on arrhythmia could not be readily accounted for.

  4. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea


    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  5. Interactions between diltiazem and inhalation anaesthetics in the isolated heart. (United States)

    Carceles, M D; Miralles, F S; Laorden, M L; Hernandez, J


    It has been postulated that inhalation anaesthetics may interfere with calcium movement across cell membranes. We have evaluated the interaction between diltiazem and the inhalation anaesthetics halothane and isoflurane on sinus automaticity in the isolated right atrium (SAIRA). Isoflurane significantly reduced atrial rate at all concentrations tested. However, halothane produced only a small but significant decrease at the higher concentrations used (1-2 v/v%). Diltiazem modified the maximal negative chronotropic response to inhalation anaesthetics. Maximum depression of SAIRA was significantly greater in the presence of two different doses of diltiazem compared with exposure to halothane and isoflurane alone. These results suggest that inhalation anaesthetics may block the influx of extracellular calcium through voltage-dependent calcium channels inhibited by diltiazem.

  6. Development of an intelligent adapter for metered dose inhalers

    Directory of Open Access Journals (Sweden)

    Zhang Mingrong


    Full Text Available To better coordinate the interaction of inhalation and aerosol release, an intelligent adapter (IA was developed for metered dose inhalers (MDIs. The adapter included three main units: a signal acquisition device, a micro-control-unit (MCU, and an actuation mechanism. To fully study the effectiveness of the intelligent adapter, an inhalation simulation experiment was done, and two bands of MDI were used for the experiment. The results indicated that, when inhalation, the intelligent adapter can press down the MDI automatically; moreover, this intelligent adapter could achieve an aerosol-release time Tr of 0.4 s for MDI A and 0.60 s for MDI B, which compares very well with the existing pure mechanical systems at 0.8 s and 1.0 s.

  7. Triple inhaled therapy for chronic obstructive pulmonary disease. (United States)

    Montuschi, Paolo; Malerba, Mario; Macis, Giuseppe; Mores, Nadia; Santini, Giuseppe


    Combining individual drugs in a single inhaler is the most convenient way to deliver triple therapy. A long-acting muscarinic receptor antagonist (LAMA) added to an inhaled corticosteroid (ICS)/long-acting β2-adrenoceptor agonist (LABA) fixed-dose combination (FDC) can improve efficacy of pharmacological treatment of patients with chronic obstructive pulmonary disease (COPD). New inhaled ICS/LABA/LAMA FDCs, including fluticasone furoate/vilanterol/umeclidinium, budesonide/formoterol/glycopyrronium and beclometasone/formoterol/glycopyrronium, are in Phase III of clinical development for COPD. Triple inhaled therapy might be particularly useful in patients with severe to very severe COPD, above all in those with peripheral blood or sputum eosinophilia, asthma-COPD overlap syndrome (ACOS) or frequent exacerbators. Future prospective studies should assess efficacy and safety of triple ICS/LABA/LAMA therapy in selected COPD phenotypes.

  8. Fiber inhalability and head deposition in rats and humans. (United States)

    Due to their dimensions and long durability, inhaled asbestos fibers clear slowly from lung airways. Retained fibers may injure the epithelium, interact with macrophages, or translocate to the interstitium to result in various respiratory diseases. Therefore, calculations of fibe...

  9. Activated nuclear factor kappa B and airway inflammation after smoke inhalation and burn injury in sheep. (United States)

    Cox, Robert A; Burke, Ann S; Jacob, Sam; Oliveras, Gloria; Murakami, Kazunori; Shimoda, Katsumi; Enkhbaatar, Perenlei; Traber, Lillian D; Herndon, David N; Traber, Daniel L; Hawkins, Hal K


    In a recent study, we have shown a rapid inflammatory cell influx across the glandular epithelium and strong proinflammatory cytokine expression at 4 hours after inhalation injury. Studies have demonstrated a significant role of nuclear factor kappa B in proinflammatory cytokine gene transcription. This study examines the acute airway inflammatory response and immunohistochemical detection of p65, a marker of nuclear factor kappa B activation, in sheep after smoke inhalation and burn injury. Pulmonary tissue from uninjured sheep and sheep at 4, 8, 12, 24, and 48 hours after inhalation and burn injury was included in the study. Following immunostaining for p65 and myeloperoxidase, the cell types and the percentage of bronchial submucosal gland cells staining for p65 and the extent of myeloperoxidase stained neutrophils in the bronchial submucosa were determined. Results indicate absence of detection of P65 before 12 hours after injury. At 12 hours after injury, strong perinuclear staining for p65 was evident in bronchial gland epithelial cells, macrophages, and endothelial cells. Bronchial submucosal gland cells showed a significant increase in the percentage of cells stained for p65 compared with uninjured animals and earlier times after injury, P macrophages, and endothelial cells. Quantitation of the neutrophil influx into the bronchial submucosa showed a significant increase compared with uninjured tissue at 24 and 48 hours after injury, P < .05. In conclusion, immunohistochemical detection of activated p65 preceded the overall inflammatory response measured in the lamina propria. However, detection of p65 did not correlate with a recent study showing rapid emigration of neutrophils at 4 hours postinjury. Together, these results suggest that p65 immunostaining may identify cells that are activated to produce proinflammatory cytokines after injury; however, the immunoexpression may not adequately reflect the temporal activation of gene transcription that may

  10. Acute effects of inhaled urban particles and ozone: lung morphology, macrophage activity, and plasma endothelin-1. (United States)

    Bouthillier, L; Vincent, R; Goegan, P; Adamson, I Y; Bjarnason, S; Stewart, M; Guénette, J; Potvin, M; Kumarathasan, P


    We studied acute responses of rat lungs to inhalation of urban particulate matter and ozone. Exposure to particles (40 mg/m3 for 4 hours; mass median aerodynamic diameter, 4 to 5 microm; Ottawa urban dust, EHC-93), followed by 20 hours in clean air, did not result in acute lung injury. Nevertheless, inhalation of particles resulted in decreased production of nitric oxide (nitrite) and elevated secretion of macrophage inflammatory protein-2 from lung lavage cells. Inhalation of ozone (0.8 parts per million for 4 hours) resulted in increased neutrophils and protein in lung lavage fluid. Ozone alone also decreased phagocytosis and nitric oxide production and stimulated endothelin-1 secretion by lung lavage cells but did not modify secretion of macrophage inflammatory protein-2. Co-exposure to particles potentiated the ozone-induced septal cellularity in the central acinus but without measurable exacerbation of the ozone-related alveolar neutrophilia and permeability to protein detected by lung lavage. The enhanced septal thickening was associated with elevated production of both macrophage inflammatory protein-2 and endothelin-1 by lung lavage cells. Interestingly, inhalation of urban particulate matter increased the plasma levels of endothelin-1, but this response was not influenced by the synergistic effects of ozone and particles on centriacinar septal tissue changes. This suggests an impact of the distally distributed particulate dose on capillary endothelial production or filtration of the vasoconstrictor. Overall, equivalent patterns of effects were observed after a single exposure or three consecutive daily exposures to the pollutants. The experimental data are consistent with epidemiological evidence for acute pulmonary effects of ozone and respirable particulate matter and suggest a possible mechanism whereby cardiovascular effects may be induced by particle exposure. In a broad sense, acute biological effects of respirable particulate matter from ambient air

  11. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle;


    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  12. Acute chemical pneumonitis caused by nitric acid inhalation: case report

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Hyung Shim; Lee, In Jae; Ko, Eun Young; Lee, Jae Young; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)


    Chemical pneumonitis induced by nitric acid inhalation is a rare clinical condition. The previously reported radiologic findings of this disease include acute permeability pulmonary edema, delayed bronchiolitis obliterans, and bronchiectasis. In very few published rare radiologic reports has this disease manifested as acute alveolar injury; we report a case of acute chemical pneumonitis induced by nitric acid inhalation which at radiography manifested as bilateral perihilar consolidation and ground-glass attenuation, suggesting acute alveolar injury.

  13. Use of sevoflurane inhalation sedation for outpatient third molar surgery.


    Ganzberg, S.; Weaver, J.; Beck, F. M.; McCaffrey, G


    This study attempted to determine if sevoflurane in oxygen inhaled via a nasal hood as a sole sedative agent would provide an appropriate level of deep sedation for outpatient third molar surgery. Twenty-four patients scheduled for third molar removal were randomly assigned to receive either nasal hood inhalation sevoflurane or an intravenous deep sedation using midazolam and fentanyl followed by a propofol infusion. In addition to measuring patient, surgeon, and dentist anesthesiologist subj...

  14. Psychomotor and cognitive effects of 15-minute inhalation of methoxyflurane in healthy volunteers: implication for post-colonoscopy care (United States)

    Nguyen, Nam Q.; Burgess, Jenna; Debreceni, Tamara L.; Toscano, Leanne


    Background and study aims: Colonoscopy with portal inhaled methoxyflurane (Penthrox) is highly feasible with low sedation risk and allows earlier discharge. It is unclear if subjects can return to highly skilled psychomotor skill task shortly after Penthrox assisted colonoscopy. We evaluated the psychomotor and cognitive effects of 15-minute inhalation of Penthrox in adults. Patients and methods: Sixty healthy volunteers (18 to 80 years) were studied on 2 occasions with either Penthrox or placebo in a randomized, double-blind fashion. On each occasion, the subject’s psychomotor function was examined before, immediately, 30, 60, 120, 180 and 240 min after a 15-minute inhalation of studied drug, using validated psychomotor tests (Digit Symbol Substitution Test (DSST), auditory reaction time (ART), eye-hand coordination (EHC) test, trail making test (TMT) and logical reasoning test (LRT). Results: Compared to placebo, a 15-minute Penthrox inhalation led to an immediate but small impairment of DSST (P < 0.001), ART (P < 0.001), EHC (P < 0.01), TMT (P = 0.02) and LRT (P = 0.04). In all subjects, the performance of all 5 tests normalized by 30 minutes after inhalation, and was comparable to that with placebo. Although increasing age was associated with a small deterioration in psychomotor testing performance, the magnitude of Penthrox effects remained comparable among all age groups. Conclusions: In all age groups, a 15-minute Penthrox inhalation induces acute but short-lasting impairment of psychomotor and cognitive performance, which returns to normal within 30 minutes , indicating that subjects who have colonoscopy with Penthrox can return to highly skilled psychomotor skills tasks such as driving and daily work the same day. PMID:27853742

  15. Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study

    Directory of Open Access Journals (Sweden)

    Goldstein Brahm


    Full Text Available Abstract Background Effects of nitric oxide (NO on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control. Patients/Methods Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals. Results Activated clotting time (ACT, prothrombin time (PT and activated partial thromboplastin time (aPTT increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11 and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12. Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group. Conclusions Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

  16. Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology. (United States)

    Nguyen, Jacques D; Aarde, Shawn M; Cole, Maury; Vandewater, Sophia A; Grant, Yanabel; Taffe, Michael A


    Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.

  17. Radioaerosol Inhalation Imaging in Bronchial Asthma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bum Soo; Park, Young Ha; Park, Jeong Mi; Chung, Myung Hee; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)


    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of {sup 99m}Tc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with {sup 99m}Tc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present

  18. Applicability of a modified MCE filter method with Button Inhalable Sampler for monitoring personal bioaerosol inhalation exposure. (United States)

    Xu, Zhenqiang; Xu, Hong; Yao, Maosheng


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

  19. Inhalers and nebulizers: which to choose and why. (United States)

    Pedersen, S


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

  20. Inhalable dust and protein exposure in soybean processing plants. (United States)

    Spies, Adri; Rees, David; Fourie, Anna M; Wilson, Kerry S; Harris-Roberts, Joanne; Robinson, Edward


    Little is known about inhalable dust concentrations in soybean processing plants in southern Africa. This project measured inhalable dust in soybean plants in the region and correlated dust measurements with total protein and soy trypsin inhibitor. Sixty-four personal inhalable dust measurements were taken in three processing plants. Levels of total protein and soy trypsin inhibitor were determined in only two of the three plants. Correlations between inhalable dust, total protein and trypsin inhibitor were determined for 44 of 64 samples. In plants' production areas, inhalable dust levels were 0.24-35.02 mg/m3 (median 2.58 mg/m3). Total protein and soy trypsin inhibitor levels were 29.41-448.82 microg/m3 (median 90.09 microg/m3) and 0.05-2.58 microg/m3 (median 0.07 microg/m3), respectively. No statistically significant correlations between presence of inhalable dust and soy trypsin inhibitor were found. Total protein and soy trypsin inhibitor were better correlated. This study indicates that total protein might be a good proxy for soybean specific protein concentrations in soybean processing plants.

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

    Directory of Open Access Journals (Sweden)

    Nave R


    Full Text Available Ruediger Nave, Helgert Mueller Nycomed: a Takeda Company, Nycomed GmbH, Konstanz, Germany Abstract: 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. Keywords: ciclesonide, asthma, small airways

  2. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies. (United States)

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


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

  3. Inhalation toxicity of (1→3-β-D glucan: recent advances

    Directory of Open Access Journals (Sweden)

    Birgitta Fogelmark


    Full Text Available To investigate the effects of (1→3-β-D-glucan after inhalation, animals were exposed to different forms of glucan and the number of lung lavage cells was determined 24 h after exposure. None of the different forms assayed caused any increase in cell numbers. In animals exposed to endotoxin, all types of cells were increased after 24 h. A simultaneous exposure to curdlan reduced this increase in a dose-related fashion. The results suggest that (1→3-β-D-glucan-related acute injury to the lung is induced by mechanisms other than those induced by inflammagenic agents such as endotoxin.

  4. Early interventions in asthma with inhaled corticosteroids. (United States)

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


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

  5. Anxiolytic-like effect of Citrus limon (L. Burm f. essential oil inhalation on mice

    Directory of Open Access Journals (Sweden)

    M.D.M. VIANA


    Full Text Available ABSTRACT Experimental in vivo study aimed to characterize the anxiolytic-like effect of the Citrus limon fruit peel’s essential oil (CLEO in animal models of anxiety, besides evaluating the viability J774.A1 cells in vitro through the MTT reduction method at the concentrations of 10 and 100 µg/mL. The anxiolytic behavior was evaluated in Swiss mice (n = 8 using the methodology of Elevated Plus-Maze (EPM and Open-Field (OF. CLEO was tested by inhalation at the doses of 100, 200, and 400 µL, and as control, animals were subjected to inhalation of the vehicle (saline solution 0.9% + Tween80® and intraperitoneal administration of diazepam (1.5 mg/kg. In the cell viability assay, it was observed that none of the concentrations showed cytotoxicity. OF test showed significant anxiolytic activity at all tested doses of OECL, compared to the control group, without changing the motor performance of the animals. Corroborating OF data, the EPM test confirmed anxiolytic activity in at least two doses of the tested oil (200 and 400 µL, justified by the number of entries and increase in the percentage of time in the open arms. The data analysis of this study evidenced that inhalation of OECL was able to induce an anxiolytic behavior in mice; however, further studies are required to ensure its safe use by the population.

  6. The rule of five for non-oral routes of drug delivery: ophthalmic, inhalation and transdermal. (United States)

    Choy, Young Bin; Prausnitz, Mark R


    The Rule of Five predicts suitability of drug candidates, but was developed primarily using orally administered drugs. Here, we test whether the Rule of Five predicts drugs for delivery via non-oral routes, specifically ophthalmic, inhalation and transdermal. We assessed 111 drugs approved by FDA for those routes of administration and found that >98% of current non-oral drugs have physicochemical properties within the limits of the Rule of Five. However, given the inherent bias in the dataset, this analysis was not able to assess whether drugs with properties outside those limits are poor candidates. Indeed, further analysis indicates that drugs well outside the Rule of Five limits, including hydrophilic macromolecules, can be delivered by inhalation. In contrast, drugs currently administered across skin fall within more stringent limits than predicted by the Rule of Five, but new transdermal delivery technologies may make these constraints obsolete by dramatically increasing skin permeability. The Rule of Five does appear to apply well to ophthalmic delivery. We conclude that although current non-oral drugs mostly have physicochemical properties within the Rule of Five thresholds, the Rule of Five should not be used to predict non-oral drug candidates, especially for inhalation and transdermal routes.

  7. Development of an acute model of inhalational melioidosis in the common marmoset (Callithrix jacchus). (United States)

    Nelson, Michelle; Dean, Rachel E; Salguero, Francisco J; Taylor, Christopher; Pearce, Peter C; Simpson, Andrew J H; Lever, Mark S


    Studies of inhalational melioidosis were undertaken in the common marmoset (Callithrix jacchus). Following exposure to an inhaled challenge with aerosolized Burkholderia pseudomallei, lethal infection was observed in marmosets challenged with doses below 10 cfu; a precise LD(50) determination was not possible. The model was further characterized using a target challenge dose of approximately 10(2) cfu. A separate pathogenesis time-course experiment was also conducted. All animals succumbed, between 27 and 78 h postchallenge. The challenge dose received and the time to the humane endpoint (1 °C below normal body temperature postfever) were correlated. The first indicator of disease was an increased core body temperature (T(c) ), at 22 h postchallenge. This coincided with bacteraemia and bacterial dissemination. Overt clinical signs were first observed 3-5 h later. A sharp decrease (typically within 3-6 h) in the T(c) was observed prior to humanely culling the animals in the lethality study. Pathology was noted in the lung, liver and spleen. Disease progression in the common marmoset appears to be consistent with human infection in terms of bacterial spread, pathology and physiology. The common marmoset can therefore be considered a suitable animal model for further studies of inhalational melioidosis.

  8. Talcum induced pneumoconiosis following inhalation of adulterated marijuana, a case report

    Directory of Open Access Journals (Sweden)

    Scheel Andreas


    Full Text Available Abstract Background Talcosis, a granulomatous inflammation of the lungs caused by inhalation of talcum dust, is a rare form of pneumoconiosis. Besides inhalative occupational exposure, intravenous abuse of adulterated drugs is a major cause for this condition. Minerals such as talcum (magnesium silicate and sand (predominant silicon dioxide are used to increase both volume and weight of illicit substances. In intravenous heroin-abuse, talcosis is a well-known complication. Here we describe a case of talcosis caused by inhalative abuse of adulterated marijuana. Clinical history A 29-year old man presented with persistent fever, dyspnea and cervical emphysema. He admitted consumption of 'cut' marijuana for several years, preferentially by water pipe smoking. Morphologic findings Lung-biopsies showed chronic interstitial lung disease, anthracotic pigments and birefringent material. Energy dispersive x-ray spectroscopy revealed silicon-containing particles (1-2 μm and fine aluminum particles ( Conclusions The exacerbated chronic interstitial lung disease in a 29-year old patient could be attributed to his prolonged abuse of talcum-adulterated marjuana by histopathology and x-ray spectroscopy. Since cannabis consumption is widely spread among young adults, it seems to be justified to raise attention to this form of interstitial pulmonary disease. Virtual slides The virtual slide(s for this article can be found here:

  9. Pulmonary toxicity of well-dispersed cerium oxide nanoparticles following intratracheal instillation and inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Morimoto, Yasuo, E-mail:; Izumi, Hiroto; Yoshiura, Yukiko; Tomonaga, Taisuke; Oyabu, Takako; Myojo, Toshihiko; Kawai, Kazuaki; Yatera, Kazuhiro [University of Occupational and Environmental Health (Japan); Shimada, Manabu; Kubo, Masaru [Hiroshima University (Japan); Yamamoto, Kazuhiro [National Institute of Advanced Industrial Science and Technology (AIST) (Japan); Kitajima, Shinichi [National Sanatorium Hoshizuka Keiaien (Japan); Kuroda, Etsushi [Osaka University, Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (Japan); Kawaguchi, Kenji; Sasaki, Takeshi [National Institute of Advanced Industrial Science and Technology (AIST) (Japan)


    We performed inhalation and intratracheal instillation studies of cerium dioxide (CeO{sub 2}) nanoparticles in order to investigate their pulmonary toxicity, and observed pulmonary inflammation not only in the acute and but also in the chronic phases. In the intratracheal instillation study, F344 rats were exposed to 0.2 mg or 1 mg of CeO{sub 2} nanoparticles. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed from 3 days to 6 months following the instillation. In the inhalation study, rats were exposed to the maximum concentration of inhaled CeO{sub 2} nanoparticles (2, 10 mg/m{sup 3}, respectively) for 4 weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were examined from 3 days to 3 months after the end of the exposure. The intratracheal instillation of CeO{sub 2} nanoparticles caused a persistent increase in the total and neutrophil number in BALF and in the concentration of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in BALF during the observation time. The inhalation of CeO{sub 2} nanoparticles also induced a persistent influx of neutrophils and expression of CINC-1, CINC-2, and HO-1 in BALF. Pathological features revealed that inflammatory cells, including macrophages and neutrophils, invaded the alveolar space in both studies. Taken together, the CeO{sub 2} nanoparticles induced not only acute but also chronic inflammation in the lung, suggesting that CeO{sub 2} nanoparticles have a pulmonary toxicity that can lead to irreversible lesions.

  10. Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

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    Winfried Möller

    Full Text Available Endotoxin (Lipopolysaccharide, LPS is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h, Interleukin-6 (peaking at 6 h, body temperature (peaking at 12 h, and CRP (peaking at 24 h. 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1 and reactive oxygen production, assessed by hydrogen peroxide (H(2O(2 in fractionated exhaled breath condensate (EBC. FEV(1 showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2O(2 induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2O(2.Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

  11. Evaluation of cariogenic potential of dry powder inhalers: A case-control study

    Directory of Open Access Journals (Sweden)

    Navneet Godara


    Full Text Available Objective: Dry powder inhalers (DPIs are commonly employed in the management of asthma and other diseases with airway obstruction. A causal relationship of DPI use and occurrence of dental caries has been speculated. The present case-control study was therefore designed to examine the potential link between dental caries and specific use of dry powder inhalers in patients with bronchial asthma. Materials and Methods: The present study was conducted on 100 asthmatic patients aged between 10 and 45 years who were using DPIs for at least one year. The control group (n = 100 was selected from non-asthmatic individuals and were matched with the study group with respect to age, gender, and socio-economic status. Results: The results revealed that asthmatic subjects exhibited higher occurrence of dental caries in comparison to control group, but the difference was statistically non-significant. The mean decayed, missing, and filled teeth (DMFT indices scores in asthmatic and control group were found to be 1.71 ± 2.34 SD and 1.46 ± 1.89 SD (P = 0.408, respectively. Likewise, the mean decayed, missing, and filled surfaces (DMFS indices scores in both the groups were 2.41 ± 3.84 SD and 2.34 ± 4.48 SD (P = 0.90. However, increased frequency of DPI use was associated with significant risk of caries (P = 0.01. It has been observed that oral rinsing after an inhaler use limited the occurrence of dental caries to a certain extent although was non significant. Conclusions: Dry powder inhaler use in patients with bronchial asthma was not associated with significant risk of dental caries.

  12. Use of portable microbial samplers for estimating inhalation exposure to viable biological agents. (United States)

    Yao, Maosheng; Mainelis, Gediminas


    Portable microbial samplers are being increasingly used to determine the presence of microbial agents in the air; however, their performance characteristics when sampling airborne biological agents are largely unknown. In addition, it is unknown whether these samplers could be used to assess microbial inhalation exposure according to the particle sampling conventions. This research analyzed collection efficiencies of MAS-100, Microflow, SMA MicroPortable, Millipore Air Tester, SAS Super 180, BioCulture, and RCS High Flow portable microbial samplers when sampling six bacterial and fungal species ranging from 0.61 to 3.14 microm in aerodynamic diameter. The efficiencies with which airborne microorganisms were deposited on samplers' collection medium were compared to the particle inhalation and lung deposition convention curves. When sampling fungi, RCS High Flow and SAS Super 180 deposited 80%-90% of airborne spores on agar - highest among investigated samplers. Other samplers showed collection efficiencies of 10%-60%. When collecting bacteria, RCS High Flow and MAS-100 collected 20%-30%, whereas other samplers collected less than 10% of these bioparticles. Comparison of samplers' collection efficiencies with particle inhalation convention curves showed that RCS High Flow and SAS Super 180 could be used to assess inhalation exposure to particles larger than 2.5 microm, such as fungal spores. Performance of RCS High Flow sampler was also reflective of the particle lung deposition pattern when sampling both bacteria and fungi. MAS-100 and SAS Super 180 matched the total deposition curve fairly well when collecting bacterial and fungi species, respectively. For other tested samplers, we observed substantial discrepancies between their performances and particle deposition efficiencies in the lung. The results show that feasibility of applying portable microbial samplers for exposure assessment depends on a particular sampler model and microbial species.

  13. Novolizer: how does it fit into inhalation therapy? (United States)

    Magnussen, Helgo


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

  14. Researches regarding the Morton ether inhaler at Massachusetts General Hospital, Boston. (United States)

    Haridas, Rajesh P; Mifflin, Jeffrey A


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

  15. The Effect of Inhalation Volume and Breath-Hold Duration on the Retention of Nicotine and Solanesol in the Human Respiratory Tract and on Subsequent Plasma Nicotine Concentrations During Cigarette Smoking

    Directory of Open Access Journals (Sweden)

    Armitage AK


    Full Text Available The influence of inhalation depth and breath-hold duration on the retention of nicotine and solanesol in the human respiratory tract and on nicotine uptake was studied in ten cigarette smokers. In a first series of experiments, the subjects took seven puffs from a 10 mg ‘tar’ yield, test cigarette and a fixed volume of air (0, 75, 250, 500 or 1000 mL, as required by the protocol was inhaled after each puff in order to give a controlled ‘depth’ of inhalation. The inhalation was drawn from a bag containing the required volume of air. Following a 2 s breath-hold, subjects exhaled normally, with the first exhalation after each puff passing through a single acidified filter pad for collection of the non-retained nicotine and solanesol. Blood samples were taken before and at intervals during and after smoking for the sessions with 0, 75 and 500 mL inhalation volumes for determination of plasma nicotine and carboxyhaemoglobin levels. Another series of experiments was conducted with a fixed inhalation volume (500 mL and two further breath-hold durations (0 and 10 s in addition to 2 s from above. Nicotine and solanesol retentions were measured for each breath-hold condition. The amounts of nicotine retained within the respiratory system, expressed as a percentage of the amount taken into the mouth, were consistently higher than the corresponding values for solanesol in all five inhalation conditions (0-1000 mL, 2 s breath-hold. Nicotine retention increased from 46.5% at zero inhalation to 99.5% at 1000 mL inhalation (2 s breath-hold and from 98.0% at zero breath-hold to 99.9% at 10 s breath-hold (500 mL inhalation. Solanesol retention increased from 34.2% at zero inhalation volume to 71.9% at 1000 mL inhalation (2 s breath-hold and from 51.8% at zero breath-hold to 87.6% at 10 s breath-hold (500 mL inhalation. Plasma nicotine decreased from pre-smoking levels after zero inhalation indicating that the nicotine retained within the mouth was poorly

  16. Pulmonary biocompatibility assessment of inhaled single-wall and multiwall carbon nanotubes in BALB/c mice. (United States)

    Ravichandran, Prabakaran; Baluchamy, Sudhakar; Gopikrishnan, Ramya; Biradar, Santhoshkumar; Ramesh, Vani; Goornavar, Virupaxi; Thomas, Renard; Wilson, Bobby L; Jeffers, Robert; Hall, Joseph C; Ramesh, Govindarajan T


    With the widespread application of carbon nanotubes (CNTs) in diverse commercial processes, scientists are now concerned about the potential health risk of occupational exposures. In this study, CNT-induced pulmonary toxicity was investigated by exposing BALB/c mice to aerosolized single-wall (SW) CNT and multiwall (MW) CNT (5 μg/g of mice) for 7 consecutive days in a nose-only exposure system. Microscopic studies showed that inhaled CNTs were homogeneously distributed in the mouse lung. The total number of bronchoalveolar lavage polymorphonuclear leukocytes recovered from the mice exposed to SWCNT and MWCNT (1.2 × 10(6) ± 0.52 and 9.87 × 10(5) ± 1.45; respectively) was significantly greater than control mice (5.46 × 10(5) ± 0.78). Rapid development of pulmonary fibrosis in mice that inhaled CNT was also confirmed by significant increases in the collagen level. The lactate dehydrogenase levels were increased nearly 2- and 2.4-fold in mice that inhaled SWCNT and MWCNT, respectively, as compared with control mice. In addition, exposure of CNTs to mice showed a significant (p CNT than in control mice. Together, this study shows that inhaled CNTs induce inflammation, fibrosis, alteration of oxidant and antioxidant levels, and induction of apoptosis-related proteins in the lung tissues to trigger cell death.

  17. A cross-sectional study to assess inhalation device handling and patient satisfaction in COPD

    Directory of Open Access Journals (Sweden)

    Miravitlles M


    Full Text Available Marc Miravitlles,1 Jéssica Montero-Caballero,2 Frank Richard,2 Salud Santos,3 Juan Luis Garcia-Rivero,4 Francisco Ortega,5 Xavier Ribera61Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 3Pulmonology Department, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Pneumology Department, Hospital de Laredo, Cantabria, Spain; 5Pneumology Department, Hospital Virgen del Rocío, Sevilla, Spain; 6Boehringer Ingelheim Pharma GmbH & Co KG, Barcelona, Spain Abstract: Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD. Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ to assess the handling and satisfaction for Respimat® Soft Mist™ Inhaler (SMI compared with the Breezhaler® dry powder inhaler (DPI among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA® (tiotropium Respimat® or with Hirobriz®/Onbrez®/Oslif® (indacaterol Breezhaler® for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ

  18. Towards the optimisation and adaptation of dry powder inhalers. (United States)

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


    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.

  19. Inhalational Steroids and Iatrogenic Cushing’s Syndrome (United States)

    A.V, Raveendran


    Bronchial asthma (BA) and Allergic rhinitis (AR) are common clinical problems encountered in day to day practice, where inhalational corticosteroids (ICS) or intranasal steroids (INS) are the mainstay of treatment. Iatrogenic Cushing syndrome (CS) is a well known complication of systemic steroid administration. ICS /INS were earlier thought to be safe, but now more and more number of case reports of Iatrogenic Cushing syndrome have been reported, especially in those who are taking cytochrome P450 (CYP 450) inhibitors. Comparing to the classical clinical features of spontaneous Cushing syndrome, iatrogenic Cushing syndrome is more commonly associated with osteoporosis, increase in intra-ocular pressure, benign intracranial hypertension, aseptic necrosis of femoral head and pancreatitis, where as hypertension, hirsuitisum and menstrual irregularities are less common. Endocrine work up shows low serum cortisol level with evidence of HPA (hypothalamo-pituitary-adrenal) axis suppression. In all patients with features of Cushing syndrome with evidence of adrenal suppression always suspect iatrogenic CS. Since concomitant administration of cytochrome P450 inhibitors in patients on ICS/INS can precipitate iatrogenic CS, avoidance of CYP450 inhibitors, its dose reduction or substitution of ICS are the available options. Along with those, measures to prevent the precipitation of adrenal crisis has to be taken. An update on ICS-/INS- associated iatrogenic CS and its management is presented here. PMID:25674177

  20. Effects of benzene inhalation on murine pluripotent stem cells. (United States)

    Cronkite, E P; Inoue, T; Carsten, A L; Miller, M E; Bullis, J E; Drew, R T


    Effects of benzene inhalation on mouse pluripotent hematopoietic stem cells have been evaluated. Male mice 8--12 wk old were exposed to 400 ppm benzene for 6 h/d, 5 d/wk, for up to 9 1/2 wk. At various time intervals exposed and control animals were killed, and cardiac blood was evaluated for changes in white blood cell (WBC) and red blood cell (RBC) content. In addition, femora and tibiae were evaluated for total marrow cellularity, stem cell content (as measured by the spleen colony technique), and the percent of stem cells in DNA synthesis (as determined by the tritiated thymidine cytocide technique). Exogenous spleen colonies grown from marrow of exposed animals were counted, identified, and scored by histological type. Exposure to benzene caused significant depressions of RBCs and WBCs throughout the exposure period, which continued for at least 14 d after exposure. Bone marrow cellularity and stem cell content were also depressed in exposed animals throughout the study. Tritiated thymidine cytocide of spleen colony-forming cells was generally increased in exposed animals, perhaps indicating a compensatory response to the reduction of circulating cells. Spleen colonies of all types were depressed after exposure to benzene. The significance of the reduction in cellularity, stem cell content, and changes in morphology of spleen colonies is discussed in relation to cellular toxicity and residual injury.

  1. Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects (United States)

    Lam, C. W.; Weir, F. W.; Williams-Cavender, K.; Tan, M. N.; Galen, T. J.; Pierson, D. L.


    Bromotrifluoromethane (Halon 1301, CBrF3), is used as a fire extinguishant in the Space Shuttle, where several scenarios, such as a fire or a faulty alarm, could lead to its discharge resulting in a Halon 1301 concentration of up to 1 percent in the cabin atmosphere. The effect of Halon 1301 on mental performance and physiologic function was investigated in a NASA-sponsored human inhalation study in which four pairs of male subjects were each exposed in a double-blind fashion for 24 hr to 1 percent Halon 1301 and to air in two exposures about 1 week apart. Blood and breath samples from the exposed subjects were collected to provide dosimetric and toxicokinetic information. Halon 1301 blood levels increased rapidly and approached a steady state within 2 hr of the beginning the exposure; the steady-state concentration was approximately 3-4.5 microg/ml. Breath samples collected during exposures closely reflected chamber concentrations. Analysis of postexposure blood samples revealed that Halon 1301 was eliminated biphasically with an average t(1/2) alpha and t(1/2) beta of 4.5 min and 200 min, respectively.

  2. Uncertainties on lung doses from inhaled plutonium. (United States)

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


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

  3. Inhalability for aerosols at ultra-low windspeeds

    Energy Technology Data Exchange (ETDEWEB)

    Sleeth, Darrah K; Vincent, James H, E-mail: jhv@umich.ed [Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, 48109 (United States)


    Most previous experimental studies of aerosol inhalability were conducted in wind tunnels for windspeeds greater than 0.5 ms-{sup 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 mum for ultra-low windspeed environments from about 0.1 to 0.5 ms{sup 1}. 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

  4. Inhalability for aerosols at ultra-low windspeeds (United States)

    Sleeth, Darrah K.; Vincent, James H.


    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

  5. Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane in rats and mice. (United States)

    Morgan, Daniel L; Nyska, Abraham; Harbo, Sam Jens; Grumbein, Sondra L; Dill, Jeffrey A; Roycroft, Joseph H; Kissling, Grace E; Cesta, Mark F


    Two-year 1-bromopropane (1-BP) inhalation studies were conducted because of the potential for widespread exposure, the lack of chronic toxicity and carcinogenicity data, and the known carcinogenicity of structurally related compounds. Male and female F344/N rats and B6C3F1/N mice were exposed by inhalation to 0, 62.5 (mice only), 125, 250, or 500 (rats only) ppm 1-BP for 6 hr/day, 5 days/week for 105 weeks. Exposure of male and female rats to 1-BP resulted in significantly increased incidences of adenomas of the large intestine and skin neoplasms. In male rats, the incidence of malignant mesothelioma of the epididymis was statistically significantly increased at 500 ppm, but the biological significance of this common lesion is unclear. Incidences of pancreatic islet adenoma in male rats were significantly increased at all concentrations relative to concurrent controls but were within the historical control range for inhalation studies. There was no evidence of carcinogenic activity of 1-BP in male B6C3F1 mice; however, significantly increased incidences of alveolar/bronchiolar neoplasms of the lung were present in female mice. Exposure to 1-BP also resulted in increased incidences of nonneoplastic lesions in the nose of rats and mice, the larynx of rats and male mice, the trachea of female rats and male and female mice, and the lungs of mice. Inflammatory lesions with Splendore Hoeppli (S-H) material were present primarily in the nose and skin of exposed male and female rats, indicating that 1-BP caused immunosuppression.

  6. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto


    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchod......BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric...

  7. Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

    Directory of Open Access Journals (Sweden)

    Ashutosh Kale


    Full Text Available We report a case of accidental cutaneous burns caused by salbutamol metered dose inhaler. A 9-year-old boy underwent dental extraction at a children's hospital and was incidentally noted to have burn injuries on dorsum of both hands. On questioning, the boy revealed that a few days ago his 14-year-old brother, who is an asthmatic, playfully sprayed his salbutamol metered dose inhaler on the back of both his hands with the inhaler's mouth piece being in direct contact with the patient's skin. On examination, there was a rectangular area of erythema with superficial peeling on the dorsum of both hands, the dimensions of which exactly matched those of the inhaler's mouthpiece. It is possible that the injury could have been a chemical burn from the pharmaceutical/preservative/propellant aerosol or due to the physical effect of severe cooling of the skin or mechanical abrasive effect of the aerosol blasts or a combination of some or all the above mechanisms. This case highlights the importance of informing children and parents of the potentially hazardous consequences of misusing a metered dose inhaler.

  8. Inhaled sodium cromoglycate in angiotensin-converting enzyme inhibitor cough. (United States)

    Hargreaves, M R; Benson, M K


    Cough is a frequent side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the effects of inhaled sodium cromoglycate in 10 patients with ACE-inhibitor cough in a double-blind crossover study. After a 2-week run-in, patients were randomised to either 2 weeks' inhaled sodium cromoglycate or placebo followed by a further 2 weeks on the other treatment. Patients kept a cough diary during each study period. Cough severity was recorded on a scale from 0 to 12. At the end of each study period the cough threshold to inhaled capsaicin was measured. 9 patients reported a reduction in cough after sodium cromoglycate. Median (range) daily cough scores during run-in and placebo periods were 3.6 (1.9-6.4) and 4.1 (0.6-8.1), respectively (p > 0.05). Median daily cough score after sodium cromoglycate was 1.8 (0.4-3; p sodium cromoglycate; and cough-reflex sensitivity to inhaled capsaicin was significantly reduced. Inhaled sodium cromoglycate is an effective treatment for ACE-inhibitor cough. Its effect may be due to suppression of afferent vagal activity.

  9. Dry powder inhalable formulations for anti-tubercular therapy. (United States)

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


    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.

  10. Rethinking the paradigm for the development of inhaled drugs. (United States)

    Pritchard, John N


    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.

  11. Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model

    Directory of Open Access Journals (Sweden)

    Sergi Consolato


    Full Text Available Abstract Background Inhalation of N-chlorotaurine (NCT, an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model. Methods Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15 or 5 ml of 0.9% NaCl (control group, n = 16 was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU, and lung samples for histology. Results Arterial pressure of oxygen (PaO2 decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388 CFU/ml (median and 25 and 75 percentiles for the NCT treated pigs, and to 250 (10; 5.5 × 105 CFU/ml for NaCl treated pigs (p = 0.4159. Conclusions Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been

  12. Intermittent inhaled corticosteroids in infants with episodic wheezing

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Hermansen, Mette Northman; Loland, Lotte;


    BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one-month-old ......BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one...... not affected by treatment. CONCLUSIONS: Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life. ( number, NCT00234390.)....

  13. A perspective on the developmental toxicity of inhaled nanoparticles

    DEFF Research Database (Denmark)

    Hougaard, Karin Sørig; Campagnolo, Luisa; Chavatte-Palmer, Pascale


    This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respirat......This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from...... the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about...

  14. Inhaled formulations and pulmonary drug delivery systems for respiratory infections. (United States)

    Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim


    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'.

  15. Influence of dose distribution on risk of lung cancer occurrence after actinide oxide inhalation; Influence de la distribution de dose sur le risque d'apparition de cancers pulmonaires apres inhalation d'oxydes d'actinides

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, P.; Dudoignon, N.; Guillet, K.; Rateau, G.; Delforge, J. [Lab. de Radiotoxicologie, CEA/DSV/DRR/SRCA, Bruyeres le Chatel (France)


    The aim of this work was to estimate risk of lung tumour occurrence after inhalation of actinide oxides from published studies and rat studies in progress. For the same delivered dose, the risk increases when homogeneity of irradiation increases, i.e., the number of particles deposited after inhalation increases (small particles and (or) low specific alpha activity). The dose-effect relationships reported appear linear up to a few gray, depending on the aerosol considered, and then the slope decreases. This slope, which corresponds with the risk, can vary over one order of magnitude de ending on the aerosol used. An effective threshold at about 1 Gy was not observed for the most homogeneous dose distributions. A dosimetric and biological approach is proposed to provide a more realistic risk estimate. (author)

  16. Inhalation a significant exposure route for chlorinated organophosphate flame retardants. (United States)

    Schreder, Erika D; Uding, Nancy; La Guardia, Mark J


    Chlorinated organophosphate flame retardants (ClOPFRs) are widely used as additive flame retardants in consumer products including furniture, children's products, building materials, and textiles. Tests of indoor media in homes, offices, and other environments have shown these compounds are released from products and have become ubiquitous indoor pollutants. In house dust samples from Washington State, U.S.A., ClOPFRs were the flame retardants detected in the highest concentrations. Two ClOPFRs, tris(1,3-dichloro-2-propyl)phosphate (TDCPP or TDCIPP) and tris(2-chloroethyl)phosphate (TCEP), have been designated as carcinogens, and there is growing concern about the toxicity of the homologue tris(1-chloro-2-propyl)phosphate (TCPP or TCIPP). In response to concerns about exposure to these compounds, the European Union and a number of U.S. states have taken regulatory action to restrict their use in certain product categories. To better characterize exposure to ClOPFRs, inhalation exposure was assessed using active personal air samplers in Washington State with both respirable and inhalable particulate fractions collected to assess the likelihood particles penetrate deep into the lungs. Concentrations of ∑ClOPFRs (respirable and inhalable) ranged from 97.1 to 1190 ng m(-3) (mean 426 ng m(-3)), with TCPP detected at the highest concentrations. In general, higher levels were detected in the inhalable particulate fraction. Total intake of ClOPFRs via the inhalation exposure route was estimated to exceed intake via dust ingestion, indicating that inhalation is an important route that should be taken into consideration in assessments of these compounds.

  17. Preclinical safety evaluation of inhaled cyclosporine in propylene glycol. (United States)

    Wang, Tao; Noonberg, Sarah; Steigerwalt, Ronald; Lynch, Maryellen; Kovelesky, Rosemary A; Rodríguez, Carlos A; Sprugel, Katherine; Turner, Nancy


    Cyclosporine inhalation solution has the potential to improve outcomes following lung transplantation by delivering high concentrations of an immunosuppressant directly to the allograft while minimizing systemic drug exposure and associated toxicity. The objective of these studies was to evaluate the potential toxicity of aerosolized cyclosporine formulated in propylene glycol when given by inhalation route to rats and dogs for 28 days. Sprague-Dawley rats received total inhaled doses of 0 (air), 0 (vehicle, propylene glycol), 7.4, 24.3, and 53.9 mg cyclosporine/kg/day. In a separate study, beagle dogs were exposed to 0, 4.4, 7.7, and 9.7 mg cyclosporine/kg/day. Endpoints used to evaluate potential toxicity of inhaled cyclosporine were clinical observations, body weight, food consumption, respiratory functions, toxicokinetics, and clinical/anatomic pathology. Daily administration of aerosolized cyclosporine did not result in observable accumulation of cyclosporine in blood or lung tissue. Toxicokinetic analysis from the rat study showed that the exposure of cyclosporine was approximately 18 times higher in the lung tissue compared to the blood. Systemic effects were consistent with those known for cyclosporine. There was no unexpected systemic toxicity or clinically limiting local respiratory toxicity associated with inhalation exposure to cyclosporine inhalation solution at exposures up to 2.7 times the maximum human exposure in either rats or dogs. There were no respiratory or systemic effects of high doses of propylene glycol relative to air controls. These preclinical studies demonstrate the safety of aerosolized cyclosporine in propylene glycol and support its continued clinical investigation in patients undergoing allogeneic lung transplantation.

  18. Challenges in inhaled product development and opportunities for open innovation. (United States)

    Forbes, Ben; Asgharian, Bahman; Dailey, Lea Ann; Ferguson, Douglas; Gerde, Per; Gumbleton, Mark; Gustavsson, Lena; Hardy, Colin; Hassall, David; Jones, Rhys; Lock, Ruth; Maas, Janet; McGovern, Tim; Pitcairn, Gary R; Somers, Graham; Wolff, Ron K


    Dosimetry, safety and the efficacy of drugs in the lungs are critical factors in the development of inhaled medicines. This article considers the challenges in each of these areas with reference to current industry practices for developing inhaled products, and suggests collaborative scientific approaches to address these challenges. The portfolio of molecules requiring delivery by inhalation has expanded rapidly to include novel drugs for lung disease, combination therapies, biopharmaceuticals and candidates for systemic delivery via the lung. For these drugs to be developed as inhaled medicines, a better understanding of their fate in the lungs and how this might be modified is required. Harmonized approaches based on 'best practice' are advocated for dosimetry and safety studies; this would provide coherent data to help product developers and regulatory agencies differentiate new inhaled drug products. To date, there are limited reports describing full temporal relationships between pharmacokinetic (PK) and pharmacodynamic (PD) measurements. A better understanding of pulmonary PK and PK/PD relationships would help mitigate the risk of not engaging successfully or persistently with the drug target as well as identifying the potential for drug accumulation in the lung or excessive systemic exposure. Recommendations are made for (i) better industry-academia-regulatory co-operation, (ii) sharing of pre-competitive data, and (iii) open innovation through collaborative research in key topics such as lung deposition, drug solubility and dissolution in lung fluid, adaptive responses in safety studies, biomarker development and validation, the role of transporters in pulmonary drug disposition, target localisation within the lung and the determinants of local efficacy following inhaled drug administration.

  19. Antitoxin Treatment of Inhalation Anthrax: A Systematic Review. (United States)

    Huang, Eileen; Pillai, Satish K; Bower, William A; Hendricks, Katherine A; Guarnizo, Julie T; Hoyle, Jamechia D; Gorman, Susan E; Boyer, Anne E; Quinn, Conrad P; Meaney-Delman, Dana


    Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax

  20. Urine concentrations of repetitive doses of inhaled salbutamol

    DEFF Research Database (Denmark)

    Elers, J; Pedersen, Lars; Henninge, J;


    We examined blood and urine concentrations of repetitive doses of inhaled salbutamol in relation to the existing cut-off value used in routine doping control. We compared the concentrations in asthmatics with regular use of beta2-agonists prior to study and healthy controls with no previous use...... of beta2-agonists. We enrolled 10 asthmatics and 10 controls in an open-label study in which subjects inhaled repetitive doses of 400 microgram salbutamol every second hour (total 1600 microgram), which is the permitted daily dose by the World Anti-Doping Agency (WADA). Blood samples were collected...

  1. Use of inhaled anticholinergic agents in obstructive airway disease. (United States)

    Restrepo, Ruben D


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

  2. Usage of inhalation devices in asthma and chronic obstructive pulmonary disease: a Delphi consensus statement.


    Ninane, Vincent; Brusselle, Guy G.; Louis, Renaud; Dupont, Lieven; Liistro, Giuseppe; De Backer,Wilfried; Schlesser, Marc; Vincken, Walter


    OBJECTIVES: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD). METHODS: In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquarti...

  3. Absorption, distribution and excretion of inhaled hydrogen fluoride in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Morris, J.B.


    Rats were subjected to whole body HF exposure for 6 hrs or to nose-only HF exposure for 1 hr. Total and/or ionic fluoride concentrations in selected tissues were determined at various times following exposure. In rats sacrificed 6 hrs after whole body exposure, dose-dependent increases in lung, plasma, and kidney total and ionic fluoride concentration occurred. Rats excreted more fluoride in the urine after whole body exposure than could be explained by the amount of HF inhaled. Considerable evidence suggests that airborne HF deposits on fur and is then ingested due to preening activity. Urinary fluoride excretion was increased by nose-only exposure. The urinary fluoride excretion accounted for approximately twice the fluoride estimated to be inhaled during exposure. Tissue fluoride concentrations were elevated immediately after nose-only exposure. Fluoride concentrations in lung and kidney returned to control levels within 12 hrs. Plasma fluoride concentration was slightly elevated 24 hrs after the start of the 1 hr exposure but was at control levels at 96 hrs. Immediately following nose-only exposure, lung ionic fluoride concentrations were less than plasma ionic fluoride concentrations suggesting that the fluoride in the lung had reached that site via plasma transport rather than by inhalation. A dose-dependent increase in plasma ionic fluoride concentration occurred after upper respiratory tract HF exposure providing strong evidence that fluoride is absorbed systemically from that site. The plasma ionic fluoride concentration after upper respiratory tract exposure was of sufficient magnitude to account for the plasma fluoride concentrations observed in intact nose-only exposed rats. (ERB)

  4. The improving of ventilometric indices using Airway Clearance Techniques Asociated with Inhalation Therapy applied to adolescents with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Bogdan Almăjan-Guţă


    Full Text Available Introduction: this study gave particular attention to respiratory damage, lung disease being the main target for developingtherapies in MV. The purpose of this study was to demonstrate the efficiency of Classical Respiratory clearance techniquescombined with Inhalation Therapy and to compare the results of using acetylcysteine with those of using Pulmozyme Therapy.Aerosol (inhalation therapy is, along with exercise and respiratory clearance techniques, the third component in thephysiotherapy of patients with CF. Material and method: the study was developed during a period of six months, in TheNational Center of Cystic Fibrosis, Clinic II of Pediatrics in the Emergency County Hospital, Timisoara. The study group consistedof 12 children with MV . This group was divided into two groups of 6 patients (group 1 and group 2. Group 1 followedinhalation treatment with acetylcysteine, and group 2 with Pulmozyme. Results: The evaluation of the results was done after 2months and 6 months since the study started, by measuring the FEV, and FVC. For the first group, that used acetylcysteine inthe inhalation therapy, we observed, after 6 months, an increase of FEV with an average of 2.08% and of FVC with 2.13%.Thegrowth of ventilometric indices were relatively accelerated in the first two months and later there was a slower growth,achieving final value. For the second group, that used Pulmozyme, the growth of ventilometric indices was significantly higher.Discussion: considering the two relatively homogeneous groups, in what concerns the values of ventilometric indices andsuperimposed infection, we believe that inhaled Pulmozyme therapy proved to be superior to acetylcysteine. Conclusions:inhalation therapy is an important part of physiotherapy for patients with cystic fibrosis. A consistent physiotherapy is probablythe most important element in preventing chronic pulmonary infection and, along with antibiotherapy, improves significantlythe prognosis and helps

  5. Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction (United States)

    Simon, Marc A.; Vanderpool, Rebecca R.; Nouraie, Mehdi; Bachman, Timothy N.; White, Pamela M.; Sugahara, Masataka; Gorcsan, John; Parsley, Ed L.; Gladwin, Mark T.


    BACKGROUND. Pulmonary hypertension (PH) is associated with poor outcomes, yet specific treatments only exist for a small subset of patients. The most common form of PH is that associated with left heart disease (Group 2), for which there is no approved therapy. Nitrite has shown efficacy in preclinical animal models of Group 1 and 2 PH, as well as in patients with left heart failure with preserved ejection fraction (HFpEF). We evaluated the safety and efficacy of a potentially novel inhaled formulation of nitrite in PH-HFpEF patients as compared with Group 1 and 3 PH. METHODS. Cardiopulmonary hemodynamics were recorded after acute administration of inhaled nitrite at 2 doses, 45 and 90 mg. Safety endpoints included change in systemic blood pressure and methemoglobin levels. Responses were also compared with those administered inhaled nitric oxide. RESULTS. Thirty-six patients were enrolled (10 PH-HFpEF, 20 Group 1 pulmonary arterial hypertension patients on background PH-specific therapy, and 6 Group 3 PH). Drug administration was well tolerated. Nitrite inhalation significantly lowered pulmonary, right atrial, and pulmonary capillary wedge pressures, most pronounced in patients with PH-HFpEF. There was a modest decrease in cardiac output and systemic blood pressure. Pulmonary vascular resistance decreased only in Group 3 PH patients. There was substantial increase in pulmonary artery compliance, most pronounced in patients with PH-HFpEF. CONCLUSIONS. Inhaled nitrite is safe in PH patients and may be efficacious in PH-HFpEF and Group 3 PH primarily via improvements in left and right ventricular filling pressures and pulmonary artery compliance. The lack of change in pulmonary vascular resistance likely may limit efficacy for Group 1 patients. TRIAL REGISTRATION. NCT01431313 FUNDING. This work was supported in part by the NIH grants P01HL103455 (to MAS and MTG), R01HL098032 (to MTG), and R01HL096973 (to MTG), and Mast Therapeutics, Inc. PMID

  6. Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge

    DEFF Research Database (Denmark)

    Koullapis, P. G.; Kassinos, S. C.; Bivolarova, Mariya Petrova


    Understanding the multitude of factors that control pulmonary deposition is important in assessing the therapeutic or toxic effects of inhaled particles. The use of increasingly sophisticated in silico models has improved our overall understanding, but model realism remains elusive. In this work......, we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200 kg/m3). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects....... Nevertheless, flow field differences due to the inlet conditions are largely smoothed out just a short distance downstream of the mouth inlet as a result of the complex geometry. Increasing the inhalation flowrate from sedentary to activity conditions left the mean flowfield structures largely unaffected...

  7. HelpDesk answers: is it safe to add long-acting β-2 agonists to inhaled corticosteroids in patients with persistent asthma? (United States)

    Townsend, Laurie; Madlon-Kay, Diane J


    Possibly. Long-acting β-2 agonists (LABAs) used in combination with inhaled corticosteroids (ICS) don't appear to increase all-cause mortality or serious adverse events in patients with persistent asthma compared with ICS alone. Studies showing an increase in catastrophic events had serious methodologic issues. A large surveillance study is ongoing.

  8. 42 CFR 84.137 - Inhalation and exhalation valves; check valves; minimum requirements. (United States)


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

  9. Quality of life and adherence to inhaled corticosteroids and tiotropium in COPD are related

    Directory of Open Access Journals (Sweden)

    Koehorst-ter Huurne K


    Full Text Available Kirsten Koehorst-ter Huurne,1 Sharina Kort,1 Job van der Palen,1,3 Wendy JC van Beurden,1 Kris LL Movig,2 Paul van der Valk,1 Marjolein Brusse-Keizer1 1Department of Pulmonary Medicine, 2Department of Clinical Pharmacy, Medisch Spectrum Twente, 3Department of Research Methodology, Measurement, and Data Analysis, University of Twente, Enschede, the Netherlands Background: Poor adherence to inhaled medications in COPD patients seems to be associated with an increased risk of death and hospitalization. Knowing the determinants of nonadherence to inhaled medications is important for creating interventions to improve adherence. Objectives: To identify disease-specific and health-related quality of life (HRQoL factors, associated with adherence to inhaled corticosteroids (ICS and tiotropium in COPD patients. Methods: Adherence of 795 patients was recorded over 3 years and was deemed optimal at >75%–≤125%, suboptimal at ≥50%–<75%, and poor at <50% (underuse or >125% (overuse. Health-related quality of life was measured with the Clinical COPD Questionnaire and the EuroQol-5D questionnaire. Results: Patients with a higher forced expiratory volume in 1 second (FEV1/vital capacity (VC (odds ratio [OR] =1.03 and ≥1 hospitalizations in the year prior to inclusion in this study (OR =2.67 had an increased risk of suboptimal adherence to ICS instead of optimal adherence. An increased risk of underuse was predicted by a higher FEV1/VC (OR =1.05. Predictors for the risk of overuse were a lower FEV1 (OR =0.49, higher scores on Clinical COPD Questionnaire-question 3 (anxiety for dyspnea (OR =1.26, and current smoking (OR =1.73. Regarding tiotropium, predictors for suboptimal use were a higher FEV1/VC (OR =1.03 and the inability to perform usual activities as asked by the EuroQol-5D questionnaire (OR =3.09. A higher FEV1/VC also was a predictor for the risk of underuse compared to optimal adherence (OR =1.03. The risk of overuse increased again with higher

  10. Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.


    Cockcroft, D. W.; Berscheid, B A


    The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (l...

  11. [Oxidative stress in pathogenesis of bronchial asthma: a method of correction by inhalation of phospholipid nanoparticles]. (United States)

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


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

  12. Effect of "rose essential oil" inhalation on stress-induced skin-barrier disruption in rats and humans. (United States)

    Fukada, Mika; Kano, Eri; Miyoshi, Michio; Komaki, Ryoichi; Watanabe, Tatsuo


    In stressed animals, several brain regions (e.g., hypothalamic paraventricular nucleus [PVN]) exhibit neuronal activation, which increases plasma adrenocorticotropic hormone (ACTH) and glucocorticoids. We previously reported that so-called "green odor" inhibits stress-induced activation of the hypothalamo-pituitary-adrenocortical axis (HPA axis) and thereby prevents the chronic stress-induced disruption of the skin barrier. Here, we investigated whether rose essential oil, another sedative odorant, inhibits the stress-induced 1) increases in PVN neuronal activity in rats and plasma glucocorticoids (corticosterone [CORT] in rats and cortisol in humans) and 2) skin-barrier disruption in rats and humans. The results showed that in rats subjected to acute restraint stress, rose essential oil inhalation significantly inhibited the increase in plasma CORT and reduced the increases in the number of c-Fos-positive cells in PVN. Inhalation of rose essential oil significantly inhibited the following effects of chronic stress: 1) the elevation of transepidermal water loss (TEWL), an index of the disruption of skin-barrier function, in both rats and humans and 2) the increase in the salivary concentration of cortisol in humans. These results suggest that in rats and humans, chronic stress-induced disruption of the skin barrier can be limited or prevented by rose essential oil inhalation, possibly through its inhibitory effect on the HPA axis.

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

    Directory of Open Access Journals (Sweden)

    Darbà J


    Full Text Available Josep Darbà,1 Gabriela Ramírez,2 Antoni Sicras,3 Pablo Francoli,4 Saku Torvinen,5 Rainel Sánchez-de la Rosa4 1Department of Economics, Universitat de Barcelona, 2BCN Health Economics and Outcomes Research SL, 3Dirección de Planificación, Badalona Serveis Assistencials, SA, Barcelona, 4Medical Department, TEVA Pharmaceutical, Madrid, Spain; 5Market Access Department, TEVA Pharmaceutical Europe BV, Amsterdam, the Netherlands 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

  14. Inhalation of butanols: changes in the cytochrome P-450 enzyme system. (United States)

    Aarstad, K; Zahlsen, K; Nilsen, O G


    After inhalation of different butanol isomers for 3 days (2000 ppm) and 5 days (500 ppm), liver and kidney parameters of the microsomal cytochrome P-450 enzyme system were increased. sec-Butanol caused the highest increase in cytochrome P-450 concentration with a 47% rise in the kidneys (500 ppm for 5 days) and 33% in the liver (2000 ppm for 3 days). A concomitant increase of the in vitro n-hexane metabolism in liver microsomes was observed with a 77% increased formation of the preneurotoxic metabolite 2-hexanol compared with control. iso-Butanol did not alter total cytochrome P-450 concentration but caused a significant 30% decrease in the formation of 2-hexanol. Inhalation of all butanols slightly decreased the enzyme levels in the lung. Changes in microsomal enzymes did not correlate with measured serum concentrations of the different butanols showing different inducing capacities among the butanol isomers themselves or the participation of metabolites in the inducing process. As a conclusion sec-butanol, probably through its metabolite methyl-ethyl-ketone, is the most potent inducer of microsomal cytochrome P-450 in liver and kidney while iso-butanol does not alter total cytochrome P-450.

  15. Concentration dependence of the embryotoxic effects of benzene inhalation in CFY rats. (United States)

    Tátrai, E; Ungváry, G; Hudák, A; Rodics, K; Lörincz, M; Barcza, G


    CFY rats were exposed to continuous benzene inhalation 24 h/day from day 7 to day 14 of gestation at 150, 450, 1500, or 3000 mg/m3 (50, 150, 500, or 1000 ppm) atmospheric concentrations. None of the benzene concentrations used proved to be teratogenic. There was no increase in the incidence of external, visceral, or skeletal malformations. Benzene inhalation at a 150 mg/m3 concentration brought about a slight toxic effect at a 450 mg/m3 concentration a more pronounced effect on both mothers and fetuses. The toxic effects were manifest as an increase in maternal mortality, circulatory damage, decreased gain in body weight, decrease in the weight of the placenta in the mothers and an increase in mortality (early and late), retardation of development (weight and skeleton) in the fetuses. No further change in the parameters was seen with further increases in benzene concentration. Avoidance of the risks of benzene exposure seems desirable before the commencement of planned pregnancy in the human.

  16. Health hazards due to the inhalation of amorphous silica. (United States)

    Merget, R; Bauer, T; Küpper, H U; Philippou, S; Bauer, H D; Breitstadt, R; Bruening, T


    Occupational exposure to crystalline silica dust is associated with an increased risk for pulmonary diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and lung cancer. This review summarizes the current knowledge about the health effects of amorphous (non-crystalline) forms of silica. The major problem in the assessment of health effects of amorphous silica is its contamination with crystalline silica. This applies particularly to well-documented pneumoconiosis among diatomaceous earth workers. Intentionally manufactured synthetic amorphous silicas are without contamination of crystalline silica. These synthetic forms may be classified as (1) wet process silica, (2) pyrogenic ("thermal" or "fumed") silica, and (3) chemically or physically modified silica. According to the different physicochemical properties, the major classes of synthetic amorphous silica are used in a variety of products, e.g. as fillers in the rubber industry, in tyre compounds, as free-flow and anti-caking agents in powder materials, and as liquid carriers, particularly in the manufacture of animal feed and agrochemicals; other uses are found in toothpaste additives, paints, silicon rubber, insulation material, liquid systems in coatings, adhesives, printing inks, plastisol car undercoats, and cosmetics. Animal inhalation studies with intentionally manufactured synthetic amorphous silica showed at least partially reversible inflammation, granuloma formation and emphysema, but no progressive fibrosis of the lungs. Epidemiological studies do not support the hypothesis that amorphous silicas have any relevant potential to induce fibrosis in workers with high occupational exposure to these substances, although one study disclosed four cases with silicosis among subjects exposed to apparently non-contaminated amorphous silica. Since the data have been limited, a risk of chronic bronchitis, COPD or emphysema cannot be excluded. There is no study

  17. Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

    Directory of Open Access Journals (Sweden)

    Radosław Świercz


    Full Text Available Background: Benzalkonium chloride (BAC is a quaternary ammonium compound (QAC toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group and 35 mg/m3 for 5 days (6 h/day and, after a 2-week interval, the animals were challenged (day 21 with BAC aerosol at the target concentration of 0 (control group and 35 mg/m3 for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs.

  18. Comparison of sarin and cyclosarin toxicity by subcutaneous, intravenous and inhalation exposure in Gottingen minipigs. (United States)

    Hulet, Stanley W; Sommerville, Douglas R; Miller, Dennis B; Scotto, Jacqueline A; Muse, William T; Burnett, David C


    Sexually mature male and female Gottingen minipigs were exposed to various concentrations of GB and GF vapor via whole-body inhalation exposures or to liquid GB or GF via intravenous or subcutaneous injections. Vapor inhalation exposures were for 10, 60 or 180 min. Maximum likelihood estimation was used to calculate the median effect levels for severe effects (ECT50 and ED50) and lethality (LCT50 and LD50). Ordinal regression was used to model the concentration × time profile of the agent toxicity. Contrary to that predicted by Haber's rule, LCT50 values increased as the duration of the exposures increased for both nerve agents. The toxic load exponents (n) were calculated to be 1.38 and 1.28 for GB and GF vapor exposures, respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GB in male minipigs were 73, 106 and 182 mg min/m(3), respectively. LCT50 values for 10-, 60 - and 180-min exposures to vapor GB in female minipigs were 87, 127 and 174 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures to vapor GF in male minipigs were 218, 287 and 403 mg min/m(3), respectively. LCT50 values for 10-, 60- and 180-min exposures in female minipigs were 183, 282 and 365 mg min/m(3), respectively. For GB vapor exposures, there was a tenuous gender difference which did not exist for vapor GF exposures. Surprisingly, GF was 2-3 times less potent than GB via the inhalation route of exposure regardless of exposure duration. Additionally GF was found to be less potent than GB by intravenous and subcutaneous routes.

  19. Inhalation toxicity and carcinogenicity studies of cobalt sulfate. (United States)

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J


    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  20. [Adrenal cortex insufficiency in children due to inhaled corticosteroids

    NARCIS (Netherlands)

    Eijkemans, M.C.J.; Otten, B.J.; Yntema, J.L.


    A 3-year-old boy was treated for asthmatic symptoms with fluticasone inhalations. Due to a flattening growth curve Cushing's syndrome was suspected and the dosage of fluticasone was gradually decreased after which the boy became less active and his appetite decreased. Another patient, a 7-year-old b

  1. Treatment with inhaled corticosteroids in asthma is too often discontinued

    NARCIS (Netherlands)

    Breekveldt-Postma, Nancy S.; Koerselman, Jeroen; Erkens, Joelle A.; van der Molen, Thys; Lammers, Jan-Willem J.; Herings, Ron M. C.


    Purpose To study persistence with inhaled corticosteroids (ICS) and its determinants in asthma-patients. Methods From the PHARMO database, asthma-patients (age <35 years) with a first dispensing for ICS in 1999-2002 and >= 2 dispensings in the first year were included. Persistence during the first y

  2. Inhaled corticosteroids in chronic obstructive pulmonary disease : a review

    NARCIS (Netherlands)

    Telenga, Eef D.; Kerstjens, Huib A. M.; Postma, Dirkje S.; ten Hacken, Nick H.; van den Berge, Maarten


    Importance of the field: Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic airflow obstruction and a progressive lung function decline. Although widely used, the efficacy of inhaled corticosteroids (ICS) in the treatment of COPD remains a matter of debate. Areas cove

  3. [Inhaled corticosteroids in patients with COPD: maintain current guidelines

    NARCIS (Netherlands)

    Heijdra, Y.F.


    The use of inhaled corticosteroids (ICS) is one of the most controversial issues in COPD treatment. There is evidence that ICS with or without long-acting beta-2-adrenergics (LABA) reduce exacerbation rates and improve the health status of severe COPD patients. The effects on FEV1 are limited and th

  4. Inhaled Antibiotics for Gram-Negative Respiratory Infections. (United States)

    Wenzler, Eric; Fraidenburg, Dustin R; Scardina, Tonya; Danziger, Larry H


    Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

  5. Characteristics of peaks of inhalation exposure to organic solvents

    NARCIS (Netherlands)

    Preller, L.; Burstyn, I.; Pater, N. de; Kromhout, H.


    Objectives: To determine which exposure metrics are sufficient to characterize 'peak' inhalation exposure to organic solvents (OS) during spraying operations. Methods: Personal exposure measurements (n = 27; duration 5-159 min) were collected during application of paints, primers, resins and glues i

  6. Inhaled budesonide for treatment of recurrent wheezing in early childhood

    DEFF Research Database (Denmark)

    Bisgaard, H; Munck, Susanne; Nielsen, J P;


    be ascribed to the active treatment. The findings indicate that young children below 3 years of age can inhale a pressurised aerosol from a spacer with a facemask. Use of topically active glucocorticosteroids with this simple device may reduce symptoms and distress in young children with moderately severe...

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

    NARCIS (Netherlands)

    Peters, S.M.; Thomassen, Y.; Fechter-Rink, E.; Kromhout, H.


    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

  8. Drug interactions between inhaled corticosteroids and enzymatic inhibitors


    Daveluy, Amélie; Raignoux, Cécile; Miremont-Salamé, Ghada; Girodet, Pierre-Olivier; Moore, Nicholas; Haramburu, Françoise; Molimard, Mathieu


    Drug interactions between inhaled corticosteroids and enzymatic inhibitors phone: +33-557-571561 (Daveluy, Amelie) (Daveluy, Amelie) Centre Regional de Pharmacovigilance, Hopital Pellegrin - 33076 - Bordeaux Cedex - FRANCE (Daveluy, Amelie) Unite 657, INSERM - Bordeaux - FRANCE (Daveluy, Amelie) Departement de Pharmacologie, CHU de Bordeaux - Bordeaux - FRANCE (Daveluy, Amelie) Centre Regional de Pharmacovigilance, Hopital Pellegrin - 33076...

  9. Extrafine inhaled corticosteroid therapy in the control of asthma

    Directory of Open Access Journals (Sweden)

    Ivancsó I


    Full Text Available István Ivancsó, Renáta Böcskei, Veronika Müller, Lilla Tamási Department of Pulmonology, Semmelweis University, Budapest, Hungary Abstract: Small airways disease plays an important role in the pathogenesis of asthma, but assessment of small airways impairment is not easy in everyday clinical practice. The small airways can be examined by several invasive and noninvasive methods, most of which can at present be used only in the experimental setting. Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways. Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation, ie, on dysfunction in both the central and distal airways in asthmatics, and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes, including nocturnal asthma, severe steroid-dependent or difficult-to-treat asthma, asthma complicated by smoking, elderly asthmatic patients and/or patients with fixed airflow obstruction, and asthmatic children. The relevant randomized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints, but there are certain clinically important endpoints for which the extrafine formulations show additional benefits. Keywords: small airways, inflammation, dysfunction, noninvasive evaluation methods, peripheral deposition


    Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

  11. Behavioral effects of subchronic inhalation of toluene in adult rats. (United States)

    Beasley, Tracey E; Evansky, Paul A; Gilbert, Mary E; Bushnell, Philip J


    Whereas the acute neurobehavioral effects of toluene are robust and well characterized, evidence for persistent effects of repeated exposure to this industrial solvent is less compelling. The present experiment sought to determine whether subchronic inhalation of toluene caused persistent behavioral changes in rats. Adult male Long-Evans rats inhaled toluene vapor (0, 10, 100, or 1000 ppm) for 6h/day, 5 days/week for 13 weeks and were evaluated on a series of behavioral tests beginning 3 days after the end of exposure. Toluene delayed appetitively-motivated acquisition of a lever-press response, but did not affect motor activity, anxiety-related behavior in the elevated plus maze, trace fear conditioning, acquisition of an appetitively-motivated visual discrimination, or performance of a visual signal detection task. Challenges with acute inhalation of toluene vapor (1200-2400 ppm for 1 h) and injections of quinpirole (0.01-0.03 mg/kg) and raclopride (0.03-0.10 mg/kg) revealed no toluene-induced latent impairments in visual signal detection. These results are consistent with a pattern of subtle and inconsistent long-term effects of daily exposure to toluene vapor, in contrast to robust and reliable effects of acute inhalation of the solvent.

  12. Infant with Altered Consciousness after Cannabis Passive Inhalation (United States)

    Zarfin, Yehoshua; Yefet, Enav; Abozaid, Said; Nasser, Wael; Mor, Tamer; Finkelstein, Yoram


    We report on an infant who was admitted to hospital with severe neurological symptoms following passive inhalation of cannabis. To date, cannabis abuse has been described almost entirely in adolescents and adults. In early childhood, however, cannabis effects were almost exclusively discussed in the context of maternal prenatal exposure, and the…

  13. Effects of Radon inhalation on physiology and disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yamaoka, Kiyonori [Central Research Inst. of Electric Power Industry, Komae, Tokyo (Japan). Komae Research Lab; Komoto, Yoshiaki


    In the first study, we administered Radon (Rn) to rabbits by inhalation and examined changes in the lipid peroxide (thiobarbituric acid reacting substances; TBARS) level, superoxide dismutase (SOD) activity and membrane fluidity in various organs to clarify the therapeutic effects of Rn. In the second study, we sprayed Rn spring water of various concentrations to rabbits to make the animals inhale them, and examined mainly the responses of biogenic amine neurotransmitters for clarifying the effects of Rn inhalation in the neuronal transmitter system. In the third study, indications for treatment at the Misasa Hot Spring, a Rn producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances after Rn inhalation. Vasodilation, alleviation of diabetic symptoms and morphine-like analgesic effects were observed, suggesting that these changes constitute part of the mechanisms of the Rn spring therapy on the above conditions. (J.P.N.)

  14. Exposure to inhalable, respirable, and ultrafine particles in welding fume. (United States)

    Lehnert, Martin; Pesch, Beate; Lotz, Anne; Pelzer, Johannes; Kendzia, Benjamin; Gawrych, Katarzyna; Heinze, Evelyn; Van Gelder, Rainer; Punkenburg, Ewald; Weiss, Tobias; Mattenklott, Markus; Hahn, Jens-Uwe; Möhlmann, Carsten; Berges, Markus; Hartwig, Andrea; Brüning, Thomas


    This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging.

  15. 40 CFR 799.9346 - TSCA 90-day inhalation toxicity. (United States)


    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA 90-day inhalation toxicity. 799.9346 Section 799.9346 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC.... Testing should be started with young healthy animals as soon as possible after weaning and...

  16. 40 CFR 799.9130 - TSCA acute inhalation toxicity. (United States)


    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA acute inhalation toxicity. 799.9130 Section 799.9130 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... 40 CFR part 792, subpart f. (3) Test procedures—(i) Preparation. Healthy young adult animals...

  17. Inhaled therapeutics for prevention and treatment of pneumonia. (United States)

    Safdar, Amar; Shelburne, Samuel A; Evans, Scott E; Dickey, Burton F


    The lungs are the most common site of serious infection owing to their large surface area exposed to the external environment and minimum barrier defense. However, this architecture makes the lungs readily available for topical therapy. Therapeutic aerosols include those directed towards improving mucociliary clearance of pathogens, stimulation of innate resistance to microbial infection, cytokine stimulation of immune function and delivery of antibiotics. In our opinion inhaled antimicrobials are underused, especially in patients with difficult-to-treat lung infections. The use of inhaled antimicrobial therapy has become an important part of the treatment of airway infection with Pseudomonas aeruginosa in cystic fibrosis and the prevention of invasive fungal infection in patients undergoing heart and lung transplantation. Cytokine inhaled therapy has also been explored in the treatment of neoplastic and infectious disease. The choice of pulmonary drug delivery systems remains critical as air-jet and ultrasonic nebulizer may deliver sub-optimum drug concentration if not used properly. In future development of this field, we recommend an emphasis on the study of the use of aerosolized hypertonic saline solution to reduce pathogen burden in the airways of subjects infected with microbes of low virulence, stimulation of innate resistance to prevent pneumonia in immunocompromised subjects using cytokines or synthetic pathogen-associated molecular pattern analogues and more opportunities for the use of inhaled antimicrobials. These therapeutics are still in their infancy but show great promise.

  18. Carbon capture and sequestration: an exploratory inhalation toxicity assessment of amine-trapping solvents and their degradation products. (United States)

    McDonald, Jacob D; Kracko, Dean; Doyle-Eisele, Melanie; Garner, C Edwin; Wegerski, Chris; Senft, Al; Knipping, Eladio; Shaw, Stephanie; Rohr, Annette


    Carbon dioxide (CO2) absorption with aqueous amine solvents is a method of carbon capture and sequestration (CCS) from flue gases. One concern is the possible release of amine solvents and degradation products into the atmosphere, warranting evaluation of potential pulmonary effects from inhalation. The CCS amines monoethanolamine (MEA), methyldiethanolamine (MDEA), and piperazine (PIP) underwent oxidative and CO2-mediated degradation for 75 days. C57bl/6N mice were exposed for 7 days by inhalation of 25 ppm neat amine or equivalant concentration in the degraded mixture. The aqueous solutions were nebulized to create the inhalation atmospheres. Pulmonary response was measured by changes in inflammatory cells in bronchoalveolar lavage fluid and cytokine expression in lung tissue. Ames mutagenicity and CHO-K1 micronucleus assays were applied to assess genotoxicity. Chemical analysis of the test atmosphere and liquid revealed complex mixtures, including acids, aldehydes, and other compounds. Exposure to oxidatively degraded MEA increased (p < 0.05) total cells, neutrophils, and lymphocytes compared to control mice and caused inflammatory cytokine expression (statistical increase at p < 0.05). MEA and CO2-degraded MEA were the only atmospheres to show statistical (p < 0.05) increase in oxidative stress. CO2 degradation resulted in a different composition, less degradation, and lower observed toxicity (less magnitude and number of effects) with no genotoxicity. Overall, oxidative degradation of the amines studied resulted in enhanced toxicity (increased magnitude and number of effects) compared to the neat chemicals.

  19. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Belinsky, S. A.; Hoover, M. D.; Bradley, P. L. [eds.


    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

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

    Energy Technology Data Exchange (ETDEWEB)

    Moisan, T.C. (Department of Preventive Medicine, Loyola University-Stritch School of Medicine, Maywood, IL (USA))


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

  1. Evidence of validity of an inhalant-craving questionnaire. (United States)

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


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

  2. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig. (United States)

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn


    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species.

  3. Inhalation or instillation of steroids for the prevention of bronchopulmonary dysplasia. (United States)

    Bassler, Dirk


    Survival of extremely preterm infants has increased over recent years, but bronchopulmonary dysplasia (BPD) remains a major cause of morbidity. In the USA, BPD is the most common chronic respiratory disorder of infancy and affects the pulmonary and overall health of 10,000 preterm infants annually. Preclinical and clinical studies suggest a crucial role for lung inflammation and host immune response in the pathogenesis of BPD. Inflammation may result from, amongst others, chorioamnionitis, postnatal infection, ventilation, and the administration of oxygen. Infants with BPD have worse long-term outcomes than those without chronic lung disease. They are more than twice as likely to be readmitted to hospital in their first year of life and, having survived their primary hospitalizations, they are more likely to die than very preterm infants without chronic lung disease. Survivors with BPD have an increased risk of neurodevelopmental impairment and their respiratory function remains compromised well into adolescence. As the first generations of extremely low birth weight (ELBW) survivors have not yet reached retirement age, there are currently no reliable data addressing the association between BPD and pulmonary diseases of the elderly such as chronic obstructive pulmonary disease. Although BPD is quite common in ELBW infants, there are infants who do not develop BPD, which supports the argument that BPD is a preventable disease, emphasizing the need for high-quality safety and efficacy prevention studies. However, according to an Institute of Medicine statement regarding pediatric drug studies, the therapeutic area that has the fewest drugs indicated for neonates is BPD. As inflammation seems to be a primary mediator of injury in the pathogenesis of BPD, anti-inflammatory agents such as steroids have long been the focus of preventive research activities. However, systemic steroids, although reducing BPD, have frequently been linked to adverse neurodevelopmental

  4. Pulmonary cystic keratinizing squamous cell lesions of rats after inhalation/instillation of different particles. (United States)

    Rittinghausen, S; Mohr, U; Dungworth, D L


    Cystic keratinizing squamous cell lesions from three inhalation studies (Study A, B, C) and one intratracheal instillation study (Study D) in rats were reclassified and a certain number of lesions examined immunohistochemically for PCNA (proliferating cell nuclear antigen) as a marker of cellular proliferation. The following classification was used: squamous cell metaplasia with marked keratinization, keratinizing cyst, cystic keratinizing epithelioma, cystic keratinizing squamous cell carcinoma, keratinizing squamous cell carcinoma and non-keratinizing squamous cell carcinoma. In study A (inhalation of coal oven exhaust and subcutaneous injection of a high dose of DB (ah)A) 49.3% of rats developed cystic keratinizing squamous cell carcinomas. Inhalation of coal oven exhaust gas together with intratracheal instillation of crocidolite or subcutaneous injection of a low dose DB(ah)A (dibenz(ah)anthracene) resulted in cystic keratinizing squamous cell carcinomas in 23% to 24% of the rats. High incidences of cystic squamous cell carcinomas in the range of 31.9% to 76.4% were observed in rats of Study B1 after a 10-months exposure to tar/pitch condensation aerosol (different B(a)P (benzo(a)pyrene) concentrations) with added carbon black in some groups. After a 20-months exposure period to the same inhalation atmospheres (Study B2) the incidence of squamous cell carcinomas was increased up to 95.8%. Exposure of rats to various concentrations of unfiltered diesel exhaust (Study C) resulted in incidences of cystic keratinizing epitheliomas ranging from 2.5% (2.5 mg/m3) to 10.7% (7.5 mg/m3). Epitheliomas were also observed in 16.2% of carbon black and 16.0% of titanium dioxide exposed rats. Only a few cystic keratinizing squamous cell carcinomas occurred. In the intratrachel instillation study (Study D) increased incidences of cystic keratinizing epitheliomas occurred in rats exposed to native diesel exhaust particles (16.7%), high dose of extracted diesel exhaust particles

  5. Control of the Free Convective Flow around the Human Body for Enhanced Inhaled Air Quality: Application to a Seat-Incorporated Personalized Ventilation Unit

    DEFF Research Database (Denmark)

    Bolashikov, Zhecho Dimitrov; Melikov, Arsen Krikor; Krenek, M.


    This paper reports on methods for control of the free convective flow around the human body, with the aim of improving inhaled air quality. The methods were studied with sea-incorporated personalized ventilation (PV)-two PV nozzles placed sideways at the head level of a seated occupant supplied...... the clean air. Another pair of control nozzles below the P V nozzles, the height of the shoulders, either provided an additional amount of clean PV air or exhausted part of the air from the free convective flow. The effectiveness of the methods for enhancing the quality of the inhaled air was studied...... of the supplied PV flows and of the control flows, etc., were performed under isothermal conditions at 20 degrees C (68 degrees F) and 26 degrees C (78.8 degrees F). The methods of control proved to be efficient and made it possible to increase the amount of clean air into inhalation at reduced personalized flow...

  6. Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats. (United States)

    March, Thomas H; Cossey, Patricia Y; Esparza, Dolores C; Dix, Kelly J; McDonald, Jacob D; Bowen, Larry E


    A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus

  7. Genuair® in chronic obstructive pulmonary disease: a novel, user-friendly, multidose, dry-powder inhaler

    NARCIS (Netherlands)

    Palen, van der Job


    Inhaled corticosteroids and bronchodilators, which are pivotal to the management of respiratory diseases, are delivered by numerous devices, including pressurized metered-dose inhalers and dry-powder inhalers. However, patient adherence to these medications is suboptimal and incorrect inhaler techni

  8. Type I interferon and pattern recognition receptor signaling following particulate matter inhalation

    Directory of Open Access Journals (Sweden)

    Erdely Aaron


    Full Text Available Abstract Background Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc – stainless steel (GMA-SS welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. Results The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10. In addition, pulmonary expression of interferon α and β and Irf7 specific pattern recognition receptors (PRR and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3 were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88 to inhalation of GMA-SS. Conclusion This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure.

  9. Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation. (United States)

    Quan-Jun, Yang; Jian-Ping, Zhang; Jian-Hua, Zhang; Yong-Long, Han; Bo, Xin; Jing-Xian, Zhang; Bona, Dai; Yuan, Zhang; Cheng, Guo


    Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic

  10. Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters. (United States)

    Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett


    The computer code LUDUC (Lung Dose Uncertainty Code), developed at the University of Florida, was originally used to investigate the range of potential doses from the inhalation of either plutonium or uranium oxides. The code employs the ICRP Publication 66 Human Respiratory Tract model; however, rather than using simple point estimates for each of the model parameters associated with particle deposition, clearance, and lung-tissue dosimetry, probability density functions are ascribed to these parameters based upon detailed literature review. These distributions are subsequently sampled within LUDUC using Latin hypercube sampling techniques to generate multiple (e.g., approximately 1,000) sets of input vectors (i.e., trials), each yielding a unique estimate of lung dose. In the present study, the dosimetry component of the ICRP-66 model within LUDUC has been extended to explicitly consider variations in the beta particle absorbed fraction due to corresponding uncertainties and biological variabilities in both source and target tissue depths and thicknesses within the bronchi and bronchioles of the thoracic airways. Example dose distributions are given for the inhalation of absorption Type S compounds of 90Sr (Tmax = 546 keV) and 90Y (Tmax = 2,284 keV) as a function of particle size. Over the particle size range of 0.001 to 1 microm, estimates of total lung dose vary by a factor of 10 for 90Sr particles and by a factor of 4 to 10 for 90Y particles. As the particle size increases to 10 microm, dose uncertainties reach a factor of 100 for both radionuclides. In comparisons to identical exposures scenarios run by the LUDEP 2.0 code, Reference Man doses for inhaled beta-emitters were shown to provide slightly conservative estimates of lung dose compared to those in this study where uncertainties in lung airway histology are considered.

  11. Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin.

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    Peggy S Lai

    Full Text Available RATIONALE: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD. These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. METHODS: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. RESULTS: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. CONCLUSIONS: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene

  12. The Regulation of Proresolving Lipid Mediator Profiles in Baboon Pneumonia by Inhaled Carbon Monoxide (United States)

    Dalli, Jesmond; Kraft, Bryan D.; Colas, Romain A.; Shinohara, Masakazu; Fredenburgh, Laura E.; Hess, Dean R.; Chiang, Nan; Welty-Wolf, Karen; Choi, Augustine M.; Piantadosi, Claude A.


    Strategies for the treatment of bacterial pneumonia beyond traditional antimicrobial therapy have been limited. The recently discovered novel genus of lipid mediators, coined “specialized proresolving mediators” (SPMs), which orchestrate clearance of recruited leukocytes and restore epithelial barrier integrity, have offered new insight into the resolution of inflammation. We performed lipid mediator (LM) metabololipidomic profiling and identification of LMs on peripheral blood leukocytes and plasma from a baboon model of Streptococcus pneumoniae pneumonia. Leukocytes and plasma were isolated from whole blood of S. pneumoniae–infected (n = 5–6 per time point) and control, uninfected baboons (n = 4 per time point) at 0, 24, 48, and 168 hours. In a subset of baboons with pneumonia (n = 3), we administered inhaled carbon monoxide (CO) at 48 hours (200–300 ppm for 60–90 min). Unstimulated leukocytes from control animals produced a proresolving LM signature with elevated resolvins and lipoxins. In contrast, serum-treated, zymosan-stimulated leukocytes and leukocytes from baboons with S. pneumoniae pneumonia produced a proinflammatory LM signature profile with elevated leukotriene B4 and prostaglandins. Plasma from baboons with S. pneumoniae pneumonia also displayed significantly reduced LM–SPM levels, including eicosapentaenoic acid–derived E-series resolvins (RvE) and lipoxins. CO inhalation increased levels of plasma RvE and lipoxins relative to preexposure levels. These results establish the leukocyte and plasma LM profiles biosynthesized during S. pneumoniae pneumonia in baboons and provide evidence for pneumonia-induced dysregulation of these proresolution programs. Moreover, these SPM profiles are partially restored with inhaled low-dose CO and SPM, which may shorten the time to pneumonia resolution. PMID:25568926

  13. Reducing the cytotoxicity of inhalable engineered nanoparticles via in situ passivation with biocompatible materials

    Energy Technology Data Exchange (ETDEWEB)

    Byeon, Jeong Hoon, E-mail: [School of Mechanical Engineering, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Park, Jae Hong; Peters, Thomas M. [Department of Occupational and Environmental Health, University of Iowa, IA 52242 (United States); Roberts, Jeffrey T., E-mail: [Department of Chemistry, Purdue University, IN 47907 (United States)


    Highlights: • The cytotoxicity of model welding particles was modulated through in situ passivation. • Model welding particles were incorporated with chitosan nanoparticles for passivation. • In vitro assay revealed that the passivated particles had a lower cytotoxicity. • Passivation with chitosan adhesive or graphite paste could also reduce cytotoxicity. • This method would be suitable for efficient reduction of inhalable toxic components. - Abstract: The cytotoxicity of model welding nanoparticles was modulated through in situ passivation with soluble biocompatible materials. A passivation process consisting of a spark discharge particle generator coupled to a collison atomizer as a co-flow or counter-flow configuration was used to incorporate the model nanoparticles with chitosan. The tested model welding nanoparticles are inhaled and that A549 cells are a human lung epithelial cell line. Measurements of in vitro cytotoxicity in A549 cells revealed that the passivated nanoparticles had a lower cytotoxicity (>65% in average cell viability, counter-flow) than the untreated model nanoparticles. Moreover, the co-flow incorporation between the nanoparticles and chitosan induced passivation of the nanoparticles, and the average cell viability increased by >80% compared to the model welding nanoparticles. As a more convenient way (additional chitosan generation and incorporation devices may not be required), other passivation strategies through a modification of the welding rod with chitosan adhesive and graphite paste did also enhance average cell viability (>58%). The approach outlined in this work is potentially generalizable as a new platform, using only biocompatible materials in situ, to treat nanoparticles before they are inhaled.

  14. Sevoflurane-Based Inhalation Induction in High-Risk Elderly Patients During Noncardiac Surgery

    Directory of Open Access Journals (Sweden)

    O. A. Grebenchikov


    Full Text Available Objective: to study the hemodynamic effects of sevoflurane during the induction of anesthesia in elderly patients at high risk for cardiac events. Subjects and methods. This study enrolled 32 patients who had a left ventricular ejection fraction of <30% during preoperative examination. According to the presumptive type of anesthesia, the patients were randomized to one of the study groups: In the sevoflurane group receiving infusion of fentanyl (1 ig^kg”‘^hr”‘, anesthesia was induced by sevoflurane at the maximum concentration of 8 vol% at first inspiration, without the respiratory circuit being prefilled. After loss of consciousness, further saturation was carried out using Fianesth, 5 vol%. Combination anesthesia (CA was that which was induced by successive administration of dormicum, ketamine, propo-fol, and fentanyl. The trachea was intubated during total myoplegia under the control of TOF (TOF-Watch, Organon, the Netherlands. Results. In all the patients under CA, its induction was made during infusion of dopamine (5 lg^kg”‘^min”‘, the dose of which had to be increased up to 10 ig • kg-1 • min-1 in 6 (75% patients. Nevertheless, there were decreases in mean blood pressure (BPmean to 46±6 mm Hg and in cardiac index (CI to 1.5±0.3 fig • kg-1 • min-1 (by 32% of the outcome value. In the sevoflurane inhalation induction group, only 3 (12.5% patients needed dopamine. Its dose producing a cardiotonic effect was near-minimal; its average maintenance infusion rate was 5.3±0.3 ig^kg”‘^min”‘. The reduction in CI was statistically insignificant; despite a 9% decrease in BPmean, this indicator in the sevoflurane group remained within acceptable ranges. Conclusion. The use of a sevoflurane-based inhalation induction technique permits higher hemodynamic stability in patients at high risk for cardiac events. Key words: inhalation induction, sevoflurane, ketamine, elderly patients.

  15. Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction. (United States)

    Belotti, Silvia; Rossi, Alessandra; Colombo, Paolo; Bettini, Ruggero; Rekkas, Dimitrios; Politis, Stavros; Colombo, Gaia; Balducci, Anna Giulia; Buttini, Francesca


    An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement.

  16. MR pulmonary ventilation information of canines inhaling aerosolized gadolinium-DTPA%应用雾化Gd DTPA获得犬肺通气信息

    Institute of Scientific and Technical Information of China (English)

    郭佑民; 吴晓明; 杨健; 王建国; 雷晓燕


    AIM:To investigate the effect of inhaling aerosolized gadolinium DTPA (Gd-DTPA) on pulmonary MR imaging in canines. METHODS:Six healthy northern dogs were performed MR scanning by using single shot turbo spin echo sequence.The changes of signal intensity (SI) in pulmonary parenchyma were respectively measured after inhaling air gas,aerosolized sodium chloride and Gd-DTPA as contrast agents.The differences of SI were compared between them. RESULTS:The SI of pulmonary parenchyma increased by 11.5%- 25.8% after inhalation of aerosolized sodium chloride solution, with no statistic difference compared to inhalation of air(t=2.798,P >0.05). Whereas the SI after inhalation of aerosolized Gd DTPA increased much higher by 42.7%- 76.8% than that after inhalation of air and aerosolized sodium chloride solution(t=4.660, P0.05);吸入 Gd-DTPA雾化颗粒后肺实质信号强度明显增加,增强幅度 42.7~ 76.8%,平均 59.2%,与吸入空气时的信号强度相比有统计学差异 (t=4.660,P< 0.05). 结论 :雾化的 Gd-DTPA可以作为一种有效的肺部 MRI增强对比剂,应用雾化 Gd DTPA来获得大型实验动物的有关肺通气信息是可行的.

  17. Ivabradine Prevents Heart Rate Acceleration in Patients with Chronic Obstructive Pulmonary Disease and Coronary Heart Disease after Salbutamol Inhalation

    Directory of Open Access Journals (Sweden)

    Uta C. Hoppe


    Full Text Available Accelerated sinus rhythm is an important side effect of inhaled salbutamol which is especially harmful in patients with chronic obstructive pulmonary disease (COPD and coronary heart disease (CHD. Cross-over, randomized, open label study design. 20 patients (18 males and two females with COPD stage II–IV and comorbide CHD NYHA class I–III were included. Spirometry with 400 mg salbutamol inhalation was performed at two consecutive days of the study. Patients in group I were prescribed 5 mg ivabradine per os 3 h before salbutamol inhalation solely on the first day of the study and patients of group II received 5 mg ivabradine only on the second day of the study. Salbutamol caused a significant increase of HR by 5.5 bpm (95% CI 0.8; 10.2, p < 0.03. After ivabradine ingestion salbutamol did not change HR significantly by −2.4 bpm (−7.0; 2.3, p = 0.33. The attenuation of HR elevation by ivabradine was significant, p < 0.01. Salbutamol alone increased FEV1 by 6.0% (2.7; 9.3, p < 0.01. This effect was not impaired by ivabradine (FEV1 increase by 7.7% (2.8; 12.6, p < 0.01 versus baseline, p = 0.5 versus no ivabradine. Ivabradine 5 mg per os prevents heart rate acceleration after inhalation of 400 mg salbutamol. Ivabradine has no impact on lung function in patients with moderate-to-very-severe COPD and CHD comorbidity.

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

    Directory of Open Access Journals (Sweden)

    Komase Y


    Full Text Available Yuko Komase,1 Akimoto Asako,2 Akihiro Kobayashi,3 Raj Sharma4 1Department of Respiratory Internal Medicine, St Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama, Kanagawa, Japan; 2MA Respiratory Department, Development and Medical Affairs Unit, GlaxoSmithKline KK, Tokyo, Japan; 3Biomedical Data Sciences Department, GlaxoSmithKline KK, Tokyo, Japan; 4Global Respiratory Franchise Medical Department, GSK, Stockley Park, UK Background: In patients receiving inhaled medication, dissatisfaction with and difficulty in using the inhaler can affect treatment adherence. The incidence of handling errors is typically higher in the elderly than in younger people. The aim of the study was to assess inhaler preference for and handling errors with the ELLIPTA® dry powder inhaler (DPI, (GSK, compared with the established BREEZHALER™, a single-dose capsule DPI (Novartis, in inhalation device-naïve Japanese volunteers aged ≥40 years. Methods: In this open-label, nondrug interventional, crossover DPI preference study comparing the ELLIPTA DPI and BREEZHALER, 150 subjects were randomized to handle the ELLIPTA or BREEZHALER DPIs until the point of inhalation, without receiving verbal or demonstrative instruction (first attempt. Subjects then crossed over to the other inhaler. Preference was assessed using a self-completed questionnaire. Inhaler handling was assessed by a trained assessor using a checklist. Subjects did not inhale any medication in the study, so efficacy and safety were not measured. Results: The ELLIPTA DPI was preferred to the BREEZHALER by 89% of subjects (odds ratio [OR] 70.14, 95% confidence interval [CI] 33.69–146.01; P-value not applicable for this inhaler for ease of use, by 63% of subjects (OR 2.98, CI 1.87–4.77; P<0.0001 for ease of determining the number of doses remaining in the inhaler, by 91% for number of steps required, and by 93% for time needed for handling the inhaler. The BREEZHALER was

  19. Health Effects Associated with Inhalation of Airborne Arsenic Arising from Mining Operations

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    Rachael Martin


    Full Text Available Arsenic in dust and aerosol generated by mining, mineral processing and metallurgical extraction industries, is a serious threat to human populations throughout the world. Major sources of contamination include smelting operations, coal combustion, hard rock mining, as well as their associated waste products, including fly ash, mine wastes and tailings. The number of uncontained arsenic-rich mine waste sites throughout the world is of growing concern, as is the number of people at risk of exposure. Inhalation exposures to arsenic-bearing dusts and aerosol, in both occupational and environmental settings, have been definitively linked to increased systemic uptake, as well as carcinogenic and non-carcinogenic health outcomes. It is therefore becoming increasingly important to identify human populations and sensitive sub-populations at risk of exposure, and to better understand the modes of action for pulmonary arsenic toxicity and carcinogenesis. In this paper we explore the contribution of smelting, coal combustion, hard rock mining and their associated waste products to atmospheric arsenic. We also report on the current understanding of the health effects of inhaled arsenic, citing results from various toxicological, biomedical and epidemiological studies. This review is particularly aimed at those researchers engaged in the distinct, but complementary areas of arsenic research within the multidisciplinary field of medical geology.

  20. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    Energy Technology Data Exchange (ETDEWEB)

    B. Bellmann; O. Creutzenberg; H. Ernst; H. Muhle [Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover (Germany)


    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m{sup 3}. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 {mu}m. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide. 7 refs., 2 tabs.

  1. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Bellmann, B; Creutzenberg, O; Ernst, H; Muhle, H, E-mail: bernd.bellmann@item.fraunhofer.d [Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Str.1, 30625 Hannover (Germany)


    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m{sup 3}. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 mum. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  2. Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust (United States)

    Bellmann, B.; Creutzenberg, O.; Ernst, H.; Muhle, H.


    The health effects of 6 different fly ash samples from biomass combustion plants (bark, wood chips, waste wood, and straw), and co-firing plants (coal, co-firing of coal and sawdust) were investigated in a 28-day nose-only inhalation study with Wistar WU rats. Respirable fractions of carbon black (Printex 90) and of titanium dioxide (Bayertitan T) were used as reference materials for positive and negative controls. The exposure was done 6 hours per day, 5 days per week at an aerosol concentration of 16 mg/m3. The MMAD of all fly ash samples and reference materials in the inhalation unit were in the range from 1.5 to 3 μm. The investigations focused predominantly on the analysis of inflammatory effects in the lungs of rats using bronchoalveolar lavage (BAL) and histopathology. Different parameters (percentage of polymorphonuclear neutrophils (PMN), interleukin-8 and interstitial inflammatory cell infiltration in the lung tissue) indicating inflammatory effects in the lung, showed a statistically significant increase in the groups exposed to carbon black (positive control), C1 (coal) and C1+BM4 (co-firing of coal and sawdust) fly ashes. Additionally, for the same groups a statistically significant increase of cell proliferation in the lung epithelium was detected. No significant effects were detected in the animal groups exposed to BM1 (bark), BM2 (wood chips), BM3 (waste wood), BM6 (straw) or titanium dioxide.

  3. Beryllium Concentrations at European Workplaces: Comparison of 'Total' and Inhalable Particulate Measurements. (United States)

    Kock, Heiko; Civic, Terence; Koch, Wolfgang


    A field study was carried out in order to derive a factor for the conversion of historic worker exposure data on airborne beryllium (Be) obtained by sampling according to the 37-mm closed faced filter cassette (CFC) 'total' particulate method into exposure concentration values to be expected when sampling using the 'Gesamtstaubprobenahmesystem' (GSP) inhalable sampling convention. Workplaces selected to represent the different copper Be work processing operations that typically occur in Germany and the EU were monitored revealing a broad spectrum of prevailing Be size distributions. In total, 39 personal samples were taken using a 37-mm CFC and a GSP worn side by side for simultaneous collection of the 'total' dust and the inhalable particulates, respectively. In addition, 20 static general area measurements were carried out using GSP, CFC, and Respicon samplers in parallel, the latter one providing information on the extra-thoracic fraction of the workplace aerosol. The study showed that there is a linear relationship between the concentrations measured with the CFC and those measured with the GSP sampler. The geometric mean value of the ratios of time-weighted average concentrations determined from GSP and CFC samples of all personal samples was 2.88. The individual values covered a range between 1 and 17 related to differences in size distributions of the Be-containing particulates. This was supported by the area measurements showing that the conversion factor increases with increasing values of the extra-thoracic fraction covering a range between 0 and 79%.

  4. Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance

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    Darbà J


    exacerbations during the study period were more likely to comply with their medication regime. The effects of DPIs toward compliance varied with the different DPIs. For instance, Accuhaler® had a greater negative effect on compliance compared to Turbuhaler® and Nexthaler® in cases of patients who suffered exacerbations. We found that GP consultations reduced the probability of medication compliance for patients treated with formoterol/budesonide combination. For retired patients, visiting the GP increased the probability of medication compliance. Conclusion: We concluded that inhaler devices influence patients’ compliance for long-term asthma medication. The impact of Accuhaler®, Turbuhaler®, and NEXThaler® on medication compliance was negative. We also identified some confounders of medication compliance such as patient’s age, severity of asthma, comorbidities, and health care costs. Keywords: adherence, inhaler devices, medication possession ratio, dry powder inhalers, pressurized metered-dose inhalers, persistence

  5. Comparison of the Pulmonary Oxidative Stress Caused by Intratracheal Instillation and Inhalation of NiO Nanoparticles when Equivalent Amounts of NiO Are Retained in the Lung. (United States)

    Horie, Masanori; Yoshiura, Yukiko; Izumi, Hiroto; Oyabu, Takako; Tomonaga, Taisuke; Okada, Takami; Lee, Byeong-Woo; Myojo, Toshihiko; Kubo, Masaru; Shimada, Manabu; Morimoto, Yasuo


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

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

    Directory of Open Access Journals (Sweden)

    Masanori Horie


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

  7. Otters Increasing - Threats Increasing

    Directory of Open Access Journals (Sweden)

    Andreas Kranz


    Full Text Available In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austria does not formally recognise this as a threat.

  8. Subchronic inhalation toxicity of benzene in rats and mice. (United States)

    Ward, C O; Kuna, R A; Snyder, N K; Alsaker, R D; Coate, W B; Craig, P H


    A subchronic inhalation toxicity study of benzene was conducted in CD-1 mice and Sprague-Dawley rats. Four groups of animals consisting of 150 mice and 50 rats/sex each were exposed to concentrations of 1, 10, 30, and 300 ppm benzene vapor, 6 hours/day, 5 days/week, for 13 weeks. Additional groups of mice and rats, of equal size, were exposed under similar conditions to filtered air and served as control groups. Thirty mice and 10 rats/sex in each group were sacrificed after 7, 14, 28, 56, and 91 days of treatment. Criteria used to evaluate exposure-related effects included behavior, body weights, organ weights, clinical pathology, gross pathology, and histopathology. Fifty animals per sex of each species were exposed concurrently for cytogenetic studies. In addition, blood serum was obtained for immunological assays. The results of these two studies will be reported separately. No consistent exposure-related trends were seen in the clinical observations and body weight data. Exposure-related clinical pathology changes were seen in the high-level (300 ppm) animals of both species. In the mice, these changes included decreases in hematocrit, total hemoglobin, erythrocyte count, leukocyte count, platelet count, myeloid/erythroid ratios, and percentage of lymphocytes. Mean cell volume, mean cell hemoglobin, glycerol lysis time, and the incidence and severity of red cell morphologic changes were increased in the mice. In the rats, decreased lymphocyte counts and a relative increase in neutrophil percentages were the only exposure-related clinical pathology alterations. Histopathologic changes were present in the thymus, bone marrow, lymph nodes, spleen, ovaries, and testes of mice exposed to 300 ppm and in most cases the incidence and severity of the lesions were greater in the males. These changes in the testes and ovaries at 300 ppm were also seen at lower concentrations, but they were of doubtful biological significance. In rats, the only exposure-related lesion

  9. Effect of a network system for providing proper inhalation technique by community pharmacists on clinical outcomes in COPD patients

    Directory of Open Access Journals (Sweden)

    Takemura M


    Full Text Available Masaya Takemura,1 Katsumi Mitsui,2 Masako Ido,2 Masataka Matsumoto,1 Misuzu Koyama,3 Daiki Inoue,1 Kazufumi Takamatsu,1 Ryo Itotani,1 Manabu Ishitoko,1 Shinko Suzuki,1 Kensaku Aihara,1 Minoru Sakuramoto,1 Hitoshi Kagioka,1 Motonari Fukui11Respiratory Disease Center, Kitano-Hospital, the Tazuke Kofukai Medical Research Institute, Osaka, Japan; 2Division of Pharmacy, Kitano-Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan; 3Kita-ku Pharmaceutical Association, Osaka, JapanIntroduction: Nonadherence to inhalation therapy is very common in patients with chronic obstructive pulmonary disease (COPD. Few data are available to support the role of community pharmacists in optimizing inhalation therapy in COPD patients. Since 2007, the Kitano Hospital and the Kita-ku Pharmaceutical Association have provided a network system for delivering correct inhalation techniques through certified community pharmacists. The effects of this network system on clinical outcomes in COPD patients were examined.Methods: A total of 88 consecutive outpatients with COPD at baseline and 82 of those 4 years later were recruited from the respiratory clinic of Kitano Hospital Medical Research Institute. Measurements included the frequency of COPD exacerbations, patients’ adherence to inhalation therapy using a five-point Likert scale questionnaire, and patients’ health status both prior to this system and 4 years later.Results: Usable information was obtained from 55 patients with COPD at baseline, and from 51 patients 4 years later. Compared with baseline values, a significant decrease was observed in the frequency of COPD exacerbations (1.5 ± 1.6 versus 0.8 ± 1.4 times/year, P = 0.017. Adherence to the inhalation regimen increased significantly (4.1 ± 0.7 versus 4.4 ± 0.8, P = 0.024, but health status was unchanged. At 4 years, of 51 COPD patients, 39 (76% patients who visited the certified pharmacies showed significantly higher medication adherence


    Goe, Alexandra; Shmalberg, Justin; Gatson, Bonnie; Bartolini, Pia; Curtiss, Jeff; Wellehan, James F X


    Prolonged anesthetic recovery times are a common clinical problem in reptiles following inhalant anesthesia. Diving reptiles have numerous adaptations that allow them to submerge and remain apneic for extended periods. An ability to shunt blood away from pulmonary circulation, possibly due to changes in adrenergic tone, may contribute to their unpredictable inhalant anesthetic recovery times. Therefore, the use of epinephrine could antagonize this response and reduce recovery time. GV-26, an acupuncture point with reported β-adrenergic and respiratory effects, has reduced anesthetic recovery times in other species. In this prospective randomized crossover study, six common snapping turtles (Chelydra serpentina) were anesthetized with inhalant isoflurane for 90 min. Turtles were assigned one of three treatments, given immediately following discontinuation of isoflurane: a control treatment (0.9% saline, at 0.1 ml/kg i.m.), epinephrine (0.1 mg/kg i.m.), or acupuncture with electrical stimulation at GV-26. Each turtle received all treatments, and treatments were separated by 48 hr. Return of spontaneous ventilation was 55% faster in turtles given epinephrine and 58% faster in the GV-26 group versus saline (P turtles displayed increases in temperature not documented in the control (P Turtles administered epinephrine showed significantly increased heart rates and end-tidal CO(2) (P turtle. Further research is necessary to evaluate the effects of concurrent GV-26 and epinephrine administration and to assess responses in other reptilian species.

  11. Carbon dioxide inhalation as a human experimental model of panic: the relationship between emotions and cardiovascular physiology. (United States)

    Leibold, Nicole K; Viechtbauer, Wolfgang; Goossens, Liesbet; De Cort, Klara; Griez, Eric J; Myin-Germeys, Inez; Steinbusch, Harry W M; van den Hove, Daniël L A; Schruers, Koen R J


    Inhaling carbon dioxide (CO2)-enriched air induces fear and panic symptoms resembling real-life panic attacks, the hallmark of panic disorder. The present study aimed to describe the emotional and cardiovascular effects evoked by inhaling CO2, taking shortcomings of previous studies into account. Healthy volunteers underwent a double inhalation of 0, 9, 17.5, and 35% CO2, according to a randomized, cross-over design. In addition to fear, discomfort, and panic symptom ratings, blood pressure and heart rate were continuously monitored. Results showed a dose-dependent increase in all self-reports. Systolic and diastolic blood pressure rose with increasing CO2 concentration, whereas heart rate results were less consistent. Diastolic blood pressure and heart rate variation correlated with fear and discomfort. Based on this relationship and the observation that the diastolic blood pressure most accurately mimicked the degree of self-reported emotions, it might serve as a putative biomarker to assess the CO2-reactivity in the future.

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

    Directory of Open Access Journals (Sweden)

    Bosnic-Anticevich S


    Full Text Available Sinthia Bosnic-Anticevich,1 Henry Chrystyn,2 Richard W Costello,3,4 Myrna B Dolovich,5 Monica J Fletcher,6 Federico Lavorini,7 Roberto Rodríguez-Roisin,8 Dermot Ryan,9,10 Simon Wan Yau Ming,2 David B Price2,11 1Woolcock Institute of Medical Research, School of Medical Sciences, University of Sydney and Sydney Local Health District, Sydney, NSW, Australia; 2Observational and Pragmatic Research Institute Pte Ltd, Singapore; 3RCSI Medicine, Royal College of Surgeons, 4RCSI Education & Research Centre, Beaumont Hospital, Beaumont, Dublin, Ireland; 5Department of Medicine, Respirology, McMaster University, ON, Canada; 6Education for Health, Warwick, UK; 7Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 8Respiratory Institute, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; 9Optimum Patient Care, Cambridge, 10Centre for Population Health Sciences, University of Edinburgh, Edinburgh, 11Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known. Aims: To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques. Methods: A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an

  13. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children.

    LENUS (Irish Health Repository)

    Ni Chroinin, Muireann


    Consensus statements recommend the addition of long-acting inhaled ss2-agonists (LABA) only in asthmatic patients who are inadequately controlled on inhaled corticosteroids (ICS). It is not uncommon for some patients to be commenced on ICS and LABA together as initial therapy.

  14. Pilot Study of Inhaled Aerosols Targeted via Magnetic Alignment of High Aspect Ratio Particles in Rabbits

    Directory of Open Access Journals (Sweden)

    Gillian E. S. Redman


    Full Text Available Recently, inhaled pharmaceutical aerosols have seen increased investigation in the treatment of lung cancer, where the inability to deliver adequate therapeutic drug concentrations to tumour sites may be overcome with improved targeted delivery to the site of the tumour. In this study, the feasibility of magnetically targeted delivery of high aspect ratio particles loaded with iron oxide nanoparticles was studied in 19 New Zealand White rabbits. Half of the exposed rabbits had a magnetic field placed externally over their right lung. Iron sensitive magnetic resonance images of the lungs were acquired to determine the iron concentrations in the right and left lung of each animal. The right/left ratio increased in the middle and basal regions of the lung where, due to the morphology of the rabbit lung, this method of targeting is most effective. With further optimization, this technique could be an effective method for increasing the dose of drug delivered to a specific site within the lung.

  15. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. (United States)

    Borron, Stephen W; Baud, Frédéric J; Mégarbane, Bruno; Bismuth, Chantal


    This chart review was undertaken to assess efficacy and safety of hydroxocobalamin for acute cyanide poisoning. Hospital records of the Fernand Widal and Lariboisière Hospitals were reviewed for intensive care unit admissions with cyanide poisoning for which hydroxocobalamin was used as first-line treatment from 1988 to 2003. Smoke inhalation cases were excluded. Hydroxocobalamin (5-20 g) was administered to 14 consecutive patients beginning a median 2.1 hours after cyanide ingestion or inhalation. Ten patients (71%) survived and were discharged. Of the 11 patients with blood cyanide exceeding the typically lethal threshold of 100 micromol/L, 7 survived. The most common hydroxocobalamin-attributed adverse events were chromaturia and pink skin discoloration. Severe cyanide poisoning of the nature observed in most patients in this study is frequently fatal. That 71% of patients survived after treatment with hydroxocobalamin suggests that hydroxocobalamin as first-line antidotal therapy is effective and safe in acute cyanide poisoning.

  16. [ECG indices in dogs after inhalation of 239Pu]. (United States)

    Karpova, V N


    Dogs of both sexes aged 2 to 4 were subjected to inhalation inoculation with polymer 239Pu or submicron 239PuO2 aerosols in amounts close to acute, subacute and chronically effective ones. ECG was recorded in standard, amplified and single leads (V3). All calculations were done by lead II. Signs of the right heart overburdening were noted in the presence of the P-pulmonale complex, deep S1 wave or cardiac electrical axis of SI-SII-SIII type. Signs of the right heart overburdening were revealed after inhalation of polimer 239Pu (70%). The absence of similar changes in damage caused by 239Pu could be attributed to its fast resorption from the lungs resulting in more moderate lesion of the respiratory organs.

  17. The inhalation of radioactive materials as related to hand contamination

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, J.C.; Rohr, R.C.


    Tests performed to determine the hazard associated with the inhalation of radioactive materials as the result of smoking with contaminated hands indicate that for dry uranium compounds adhering to the palmar surfaces of the hands, approximately 1.0% of the material may be transferred to a cigarette, and that of this approximately 0.2% may appear in the smoke which is inhaled. Most of the contamination originally placed in a cigarette was found in the ash, and only 11% of the material was not recovered following burning; approximately half of this loss may be attributed to normal losses inherent in the analytical process, the recovery efficiency for which was found by supplementary experiments to be 95%.

  18. Inhalation Toxicology Research Institute Site Environmental report, 1994

    Energy Technology Data Exchange (ETDEWEB)



    The Inhalation Toxicology Research Institute (ITRI) was constructed in 1960 with the initial purpose of studying human health hazards of inhaling airborne radioactive fission products; its scope was broadened to cover other airborne materials. ITRI has in place an extensive radiological and nonradiological environmental monitoring program which monitors air emissions, groundwater, soil and ambient air around the facility. ITRI is in compliance with air quality and hazardous waste regulations; however, sewage lagoons remain from previous operations. Remediation activities have been begun or are scheduled to begin on these lagoons and on low-level radioactive liquid waste evaporation ponds. Except for the issues mentioned, ITRI is in compliance with all other federal, state, and local regulations.

  19. Role of inhaled amphotericin in allergic bronchopulmonary aspergillosis

    Directory of Open Access Journals (Sweden)

    I S Sehgal


    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is an immunological pulmonary disorder caused by immune reactions mounted against the ubiquitous fungus Aspergillus fumigatus. The disease clinically manifests with poorly controlled asthma, hemoptysis, systemic manifestations like fever, anorexia and weight loss, fleeting pulmonary opacities and bronchiectasis. The natural course of the disease is characterized by repeated episodes of exacerbations. Almost 30-40% of the patients require prolonged therapy, which currently consists of corticosteroids and anti-fungal azoles; both these agents have significant adverse reactions. Amphotericin B administered via the inhaled route can achieve a high concentration in the small airways with minimal systemic side-effects. Nebulized amphotericin B has been used in the management of invasive pulmonary aspergillosis. The aim of this review is to study the utility of inhaled amphotericin in ABPA.

  20. Use of sevoflurane inhalation sedation for outpatient third molar surgery. (United States)

    Ganzberg, S; Weaver, J; Beck, F M; McCaffrey, G


    This study attempted to determine if sevoflurane in oxygen inhaled via a nasal hood as a sole sedative agent would provide an appropriate level of deep sedation for outpatient third molar surgery. Twenty-four patients scheduled for third molar removal were randomly assigned to receive either nasal hood inhalation sevoflurane or an intravenous deep sedation using midazolam and fentanyl followed by a propofol infusion. In addition to measuring patient, surgeon, and dentist anesthesiologist subjective satisfaction with the technique, physiological parameters, amnesia, and psychomotor recovery were also assessed. No statistically significant difference was found between the sevoflurane and midazolam-fentanyl-propofol sedative groups in physiological parameters, degree of amnesia, reported quality of sedation, or patient willingness to again undergo a similar deep sedation. A trend toward earlier recovery in the sevoflurane group was identified. Sevoflurane can be successfully employed as a deep sedative rather than a general anesthetic for extraction of third molars in healthy subjects.

  1. Development of high efficiency ventilation bag actuated dry powder inhalers. (United States)

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


    New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70-80% with fine particle fractions ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs.

  2. The use of computational approaches in inhaler development. (United States)

    Wong, William; Fletcher, David F; Traini, Daniela; Chan, Hak-Kim; Young, Paul M


    Computational Fluid Dynamics (CFD) and Discrete Element Modelling (DEM) studies relevant to inhaled drug delivery are reviewed. CFD is widely used in device design to determine airflow patterns and turbulence levels. CFD is also used to simulate particles and droplets, which are subjected to various forces, turbulence and wall interactions. These studies can now be performed routinely because of the availability of commercial software containing high quality turbulence and particle models. DEM allows for the modelling of agglomerate break-up upon interaction with a wall or due to shear in the flow. However, the computational cost is high and the number of particles that can be simulated is minimal compared with the number present in typical inhaled formulations. Therefore DEM is currently limited to fundamental studies of break-up mechanisms. With decreasing computational limitations, simulations combining CFD and DEM that can address outstanding issues in agglomerate break-up and dispersion will be possible.

  3. Weaning of inhaled nitric oxide: is there a best strategy?


    Anita M. Ware; Golombek, Sergio G


    Background: Inhaled nitric oxide (iNO) has been used in the treatment of pulmonary hypertension in neonates for many years. iNO was approved by the FDA in 1999 for hypoxic respiratory failure (HRF) in term and near term infants, defined as > 34 weeks gestational age (GA). iNO is used for persistent pulmonary hypertension of the newborn (PPHN), secondary pulmonary hypertension caused by congenital heart disease (CHD), congenital diaphragmatic hernia (CDH), meconium aspiration syndrome (MAS)...

  4. Inhalation Toxicology Research Institute Annual Report, 1992-1993 (United States)


    the following: (1) Theories implicating aluminum and other airborne, inhaled environmental toxicants as causal in Alzheimers and related, including the aluminum delivery tube, bottom surface, impactor cone, impaction plate (planchet), brass tube, and fluoropore backup filter, were...The assignment of the fuel element to the category of solids is valid because the fuel element is an alloy of aluminum and enriched uranium and as

  5. Occupational asthma caused by inhalation of bovine serum albumin powder


    Choi, Gil-Soon; Kim, Joo-Hee; Lee, Haet-Nim; Sung, Jun-Mo; Lee, Jin-Woo; Park, Hae-Sim


    Bovine serum albumin (BSA), which is present in bovine plasma, is one of the major allergens affecting patients with food allergies induced by milk and meat. It is also commonly used in research laboratories. Although some reports have documented food allergies associated with BSA, BSA-induced occupational asthma has not been reported. We report a case of occupational asthma and rhinitis in a laboratory worker caused by the inhalation of BSA powder, in which an IgE-mediated response was sugge...

  6. Inhalation Exposure Input Parameters for the Biosphere Model

    Energy Technology Data Exchange (ETDEWEB)

    K. Rautenstrauch


    This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the Technical Work Plan for Biosphere Modeling and Expert Support (BSC 2004 [DIRS 169573]). This analysis report defines and justifies values of mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception.

  7. 5-Day repeated inhalation and 28-day post-exposure study of graphene. (United States)

    Shin, Jae Hoon; Han, Sung Gu; Kim, Jin Kwon; Kim, Boo Wook; Hwang, Joo Hwan; Lee, Jong Seong; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Keun Soo; Lee, Heon Sang; Song, Nam Woong; Ahn, Kangho; Yu, Il Je


    Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concentration (0.68 ± 0.14 mg/m(3) graphene) and (3) high concentration (3.86 ± 0.94 mg/m(3) graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body weights or organ weights of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was observed in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was observed in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concentrations and time points used in this study.

  8. Steroid-decorated antibiotic microparticles for inhaled anti-infective therapy. (United States)

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Zhao, Yanli; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B H


    Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention. Unfortunately, no combined steroid-antibiotic dry powder formulation is available commercially or has been reported in the academic literature. The aim of this work was hence to develop a novel steroid-antibiotic dry powder inhaler formulation [ciprofloxacin hydrochloride (CIP) and beclomethasone dipropionate (BP)] for inhaled anti-infective therapy. The spray-dried powder was of respirable size (d50 of ∼2.3 μm), partially crystalline and had BP preferentially deposited on the particle surface. Favorably, when formulated as a binary mix, both CIP and BP showed much higher drug release and fine particle fractions (of the loaded dose) over their singly delivered counterparts, and had robust activity against the respiratory tract infection-causing bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

  9. Rose oil inhalation protects against formaldehyde-induced testicular damage in rats. (United States)

    Köse, E; Sarsılmaz, M; Taş, U; Kavaklı, A; Türk, G; Özlem Dabak, D; Sapmaz, H; Ögetürk, M


    In this experimental study, harmful effects of formaldehyde (FA) inhalation on sperm concentration, sperm quality, serum testosterone levels and the rat testes were investigated. In addition, the possible protective effects of rose oil against to these harmful effects were evaluated. For this purpose, 21 albino-Wistar rats were used. The rats in Group I were used as control group. When the rats of Group II were exposed FA (10 ppm/1 h) for 35 days, the rats of Group III inhalated rose oil (1 ml/1 h) after FA. The epididymal tissues were taken for sperm analysing and the testes were removed for histological examination. In addition, testosterone levels were determined from the blood samples. Although the testosterone levels, the epididymal sperm concentration, and the progressive sperm motility significantly decreased, the abnormal sperm rate significantly increased in the Group II when compared to Group I. In the Group III, these damages were seen less. When the rats in the Group II compared with the control group, there were serious histological damages. In the Group III, it was determined that the histological changes were less than group II. It can be expressed that serious damages occurred via formaldehyde exposure in male reproductive system and that the rose oil had protective effects against these damages.

  10. Inhaled sildenafil as an alternative to oral sildenafil in the treatment of pulmonary arterial hypertension (PAH). (United States)

    Rashid, Jahidur; Patel, Brijeshkumar; Nozik-Grayck, Eva; McMurtry, Ivan F; Stenmark, Kurt R; Ahsan, Fakhrul


    The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH. Thus, we prepared porous PLGA particles of sildenafil using a water-in-oil-in-water double emulsion solvent evaporation method with polyethyleneimine (PEI) as a porosigen and characterized the formulations for surface morphology, respirability, in-vitro drug release, and evaluated for in vivo absorption, alveolar macrophage uptake, and safety. PEI increased the particle porosity, drug entrapment, and produced drug release for 36h. Fluorescent particles showed reduced uptake by alveolar macrophages. The polymeric particles were safe to rat pulmonary arterial smooth muscle cell and to the lungs, as evidenced by the cytotoxicity assay and analyses of the injury markers in the bronchoalveolar lavage fluid, respectively. Intratracheally administered sildenafil particles elicited more pulmonary specific and sustained vasodilation in SUGEN-5416/hypoxia-induced PAH rats than oral, intravenous, or intratracheal plain sildenafil did, when administered at the same dose. Overall, true to the hypothesis, this study shows that inhaled PLGA particles of sildenafil can be administered, as a substitute for oral form of sildenafil, at a reduced dose and longer dosing interval.

  11. Inhalation of primary motor vehicle emissions: Effects of urbanpopulation and land area

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Julian D.; McKone, Thomas E.; Nazaroff, William W.


    Urban population density can influence transportation demand, as expressed through average daily vehicle-kilometers traveled per capita (VKT). In turn, changes in transportation demand influence total passenger vehicle emissions. Population density can also influence the fraction of total emissions that are inhaled by the exposed urban population. Equations are presented that describe these relationships for an idealized representation of an urban area. Using analytic solutions to these equations, we investigate the effect of three changes in urban population and urban land area (infill, sprawl, and constant-density growth) on per capita inhalation intake of primary pollutants from passenger vehicles. The magnitude of these effects depends on density-emissions elasticity ({var_epsilon}{sub e}), a normalized derivative relating change in population density to change in vehicle emissions. For example, if urban population increases, per capita intake is less with infill development than with constant-density growth if {var_epsilon}{sub e} is less than -0.5, while for {var_epsilon}{sub e} greater than -0.5 the reverse is true.

  12. Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

    Directory of Open Access Journals (Sweden)

    Gopala Krishna Murthy Talasila


    Full Text Available Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

  13. Minimizing variability of cascade impaction measurements in inhalers and nebulizers. (United States)

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


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

  14. Capsaicin inhalation in man and the effects of sodium cromoglycate. (United States)

    Collier, J. G.; Fuller, R. W.


    The inhalation of capsaicin for 1 min, delivered as an aerosol by nebulising solutions of capsaicin at concentrations of 2-65 mumol 1(-1), caused dose-dependent coughing in normal volunteers and subjects with mild asthma. Capsaicin did not cause a feeling of breathlessness, and had no effect on forced expiratory volume in 1 s (FEV1) measured at the 1st, 5th and 9th min after the challenge was completed. Coughing started within seconds of applying the face mask, continued throughout the minute of capsaicin inhalation, and stopped within seconds of the mask being removed. In any one subject the number of coughs was reproducible when repeated on the same day or after an interval of several days. Experiments using local anaesthesia applied to the buccal mucosa or larynx indicated that the cough was caused by the stimulation of capsaicin-sensitive nerve terminals situated in the larynx. Cough response was not altered by the prior inhalation of sodium cromoglycate. PMID:6423016

  15. Maternal and fetal effects after inhalation of the herbicide flumetralin

    Directory of Open Access Journals (Sweden)

    Priscila Boneventi


    Full Text Available Farm workers at Brazilian tobacco plantations are frequently exposed to toxic chemicals and eventually became contaminated with these products. Flumetralin is a inhibitor of axillary bud growth on tobacco and the effects of gestational exposure should be investigated since many pesticides cross the placental barrier and cause birth defects. The aim of this study was to investigate maternal and fetal effects caused by inhalation of Flumetralin. Pregnant Swiss mice inhaled Flumetralin for 10 or 20 minutes on the seventh day of pregnancy. On the 18th day, animals were euthanized and subjected to laparotomy for removal of the uterus and embryos. The uterus was weighed and the embryos were examined. Fetuses of both treatments showed visceral changes in the uterus, kidney and liver. Skeletal abnormalities included hydrocephalus and incomplete skull ossification in both groups. In addition, the treatment of 20 minutes exposure caused anomalies in the occipital bone and the 13rd rib besides internal bleeding. There was reduction in maternal weight gain and impaired intrauterine development of the fetus. The weight of heart, liver, kidneys and testicles of fetuses were significantly decreased. Inhalation of flumetralin proved to be potentially teratogenic in both treatments, with greater damage in the group treated for 20 minutes.

  16. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. (United States)

    Bashoura, L; Gupta, S; Jain, A; Couriel, D R; Komanduri, K V; Eapen, G A; Safdar, A; Broglio, K R; Adachi, R; Dickey, B F


    Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 microg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.

  17. White phosphorus burns and arsenic inhalation: a toxic combination. (United States)

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


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

  18. Health hazards due to the inhalation of amorphous silica

    Energy Technology Data Exchange (ETDEWEB)

    Merget, R.; Bruening, T. [Research Institute for Occupational Medicine (BGFA), Bochum (Germany); Bauer, T. [Bergmannsheil, University Hospital, Department of Internal Medicine, Division of Pneumonology, Allergology and Sleep Medicine, Bochum (Germany); Kuepper, H.U.; Breitstadt, R. [Degussa-Huels Corp., Wesseling (Germany); Philippou, S. [Department of Pathology, Augusta Krankenanstalten, Bochum (Germany); Bauer, H.D. [Research Institute for Hazardous Substances (IGF), Bochum (Germany)


    Occupational exposure to crystalline silica dust is associated with an increased risk for pulmonary diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and lung cancer. This review summarizes the current knowledge about the health effects of amorphous (non-crystalline) forms of silica. The major problem in the assessment of health effects of amorphous silica is its contamination with crystalline silica. This applies particularly to well-documented pneumoconiosis among diatomaceous earth workers. Intentionally manufactured synthetic amorphous silicas are without contamination of crystalline silica. These synthetic forms may be classified as (1) wet process silica, (2) pyrogenic (''thermal'' or ''fumed'') silica, and (3) chemically or physically modified silica. According to the different physico-chemical properties, the major classes of synthetic amorphous silica are used in a variety of products, e.g. as fillers in the rubber industry, in tyre compounds, as free-flow and anti-caking agents in powder materials, and as liquid carriers, particularly in the manufacture of animal feed and agrochemicals; other uses are found in toothpaste additives, paints, silicon rubber, insulation material, liquid systems in coatings, adhesives, printing inks, plastisol car undercoats, and cosmetics. Animal inhalation studies with intentionally manufactured synthetic amorphous silica showed at least partially reversible inflammation, granuloma formation and emphysema, but no progressive fibrosis of the lungs. Epidemiological studies do not support the hypothesis that amorphous silicas have any relevant potential to induce fibrosis in workers with high occupational exposure to these substances, although one study disclosed four cases with silicosis among subjects exposed to apparently non-contaminated amorphous silica. Since the data have been limited, a risk of chronic bronchitis, COPD or

  19. Impact of extrafine formulations of inhaled corticosteroids/long-acting beta-2 agonist combinations on patient-related outcomes in asthma and COPD

    Directory of Open Access Journals (Sweden)

    Scichilone N


    /formoterol extrafine treatment in comparison with equivalent nonextrafine inhaled corticosteroids/long-acting beta-2 agonist (ICS/LABA combinations. These improvements are associated with improved lung function and clinical outcomes, along with reduced systemic exposure to inhaled corticosteroids. The increased knowledge in the pathophysiology of the peripheral airways may lead to identify specific phenotypes of obstructive lung diseases that would mostly benefit from the treatments specifically targeting the peripheral airways.Keywords: COPD, asthma, inhalational therapy, small airways

  20. Tobramycin Inhalation Powder™: a novel drug delivery system for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis. (United States)

    Parkins, Michael D; Elborn, J Stuart


    Lung disease in cystic fibrosis (CF) is typified by the development of chronic airways infection culminating in bronchiectasis and progression to end-stage respiratory disease. Pseudomonas aeruginosa, a ubiquitous gram-negative bacteria, is the archetypical CF pathogen and is associated with an accelerated clinical decline. The development and widespread use of chronic suppressive aerosolized antibacterial therapies, in particular Tobramycin Inhalation Solution (TIS), in CF has contributed to reduced lung function decline and improved survival. However, the requirement for the aerosolization of these agents through nebulizers has been associated with increased treatment burden, reduced quality of life and remain a barrier to broader uptake. Tobramycin Inhalation Powder (TIP™) has been developed by Novartis with the express purpose of delivering the same benefits as TIS in a time-effective manner. Administered via the T-326™ (Novartis) Inhaler in four individual 28-mg capsules, TIP can be administered in a quarter of the time of traditional nebulizers and is inherently portable. In clinical studies, TIP has been shown to be safe, result in equivalent or superior reductions in P. aeruginosa sputum density and produce similar improvements in pulmonary function. TIP offers significant advantages in time saving, portability and convenience over traditional nebulized TIS with comparable clinical outcomes for individuals with CF.

  1. Pulmonary Toxicity of a Formulated Preparation of Fenvalerate in Rats Subchronically Exposed by Nose Only Inhalation for 90 Days

    Institute of Scientific and Technical Information of China (English)


    Objective The pulmonary toxicity of a commercially available formulated preparation of Fenvalerate (Fen), a synthetic pyrethroid has been studied in rats following subchronic nose only inhalation exposure route. Method  Adult male rats were exposed to Fen for 4h/day, 5 days a week for 90 days by using Flow Past Dynamic Nose only Inhalation Chamber. Results Fen exposed rats showed a significant increase in enzymatic activities of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and γ-glutamyl transferase (γ-GT) which are considered as biochemical indicators of pulmonary damage. The concomitant histopathological examination of Fen exposed rats' lung revealed inflammatory changes viz., influx of mononuclear cells admixed with a few giant cells in alveolar lumen, hypetrophied bronchiolar and alveolar epithelial lining cells and presence of edematous fluid in alveolar lumen alongwith congested parenchymatous blood vessels. Conclusion These results for the first time indicate the pulmonary toxic effects of a commonly used formulated Fen preparation by using rat model and nose only inhalation as the route of exposure.

  2. The effect of carrier particle size on adhesion, content uniformity and inhalation performance of budesonide using dry powder inhalers


    Kaialy, Waseem; Larhrib, El Hassan; Nokhodchi, Ali


    Dry Powder Inhalers (DPIs) are the result of the development of two technologies: powder technology and device technology. Particle deposition in the respiratory tract is affected by many aerosol particle properties such as particle size, shape, density, charge, and hygroscopicity.1 In particular, particle size is of great importance as it is known that particleparticle interactions within DPI formulations are related to van der Waals forces. Therefore, particle size is the mos...

  3. Inhalation Exposure Input Parameters for the Biosphere Model

    Energy Technology Data Exchange (ETDEWEB)

    M. Wasiolek


    This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This

  4. Understanding allergic asthma from allergen inhalation tests (United States)

    Cockcroft, Donald W; Hargreave, Fredrick E; O’Byrne, Paul M; Boulet, Louis-Philippe


    The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors’ involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic) airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta2-agonist-induced increase in airway response to allergen (including eosinophilic inflammation), advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a muticentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma. PMID:17948142

  5. Additional histopathologic examination of the lungs from a 3-month inhalation toxicity study with multiwall carbon nanotubes in rats. (United States)

    Treumann, Silke; Ma-Hock, Lan; Gröters, Sibylle; Landsiedel, Robert; van Ravenzwaay, Bennard


    For hazard assessment of multiwalled carbon nanotubes (MWCNTs), a 90-day inhalation toxicity study has been performed with Nanocyl NC 7000 in accordance with OECD 413 test guideline. MWCNTs produced no systemic toxicity. However, increased lung weights, multifocal granulomatous inflammation, diffuse histiocytic and neutrophilic infiltrates, and intra-alveolar lipoproteinosis were observed in lung and lung-associated lymph nodes at 0.5 and 2.5mg/m(3). Additional investigations of the lungs were performed, including special stains for examination of connective tissue, and electron microscopy was performed to determine the location of the MWCNTs. The alveolar walls revealed no increase of collagen fibers, whereas within the microgranulomas a slight increase of collagen fibers was observed. The pleura did not reveal any increase in collagen fibers. Only a slight increase in reticulin fibers in the alveolar walls in animals of the 0.5 and 2.5mg/m(3) concentration group was noted. In the 0.1mg/m(3) group, the only animal revealing minimal granulomas exhibited a minimal increase in collagen within the granuloma. No increase in reticulin was observed. Electron microscopy demonstrated entangled MWCNTs within alveolar macrophages. Occasionally electron dense particles/detritus were observed within membrane-bound vesicles (interpreted as phagosomes), which could represent degraded MWCNTs. If so, MWCNTs were degradable by alveolar macrophages and not persistent within the lung. Inhalation of MWCNTs caused granulomatous inflammation within the lung parenchyma but not the pleura in any of the concentration groups. Thus, there are some similarities to effects caused by inhaled asbestos, but the hallmark effects, namely pleural inflammation and/or fibrosis leading to mesotheliomas, are absent.

  6. Seat headrest-incorporated personalized ventilation: Thermal comfort and inhaled air quality

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor; Ivanova, T.; Stefanova, G.


    and a decreased risk of airborne cross-infection when SHPV is used. Subjects assessed the air movement and the cooling provided by the SHPV as acceptable. Acceptability was unchanged over in time and increased with the increase of the air temperature. No draught was reported. The SHPV can be used in spaces where......The performance of personalized ventilation with seat headrest-mounted air supply terminal devices (ATD), named seat headrest personalized ventilation (SHPV), was studied. Physical measurements using a breathing thermal manikin were taken to identify its ability to provide clean air to inhalation...... depending on design, shape, size and positioning of the ATD, flow rate and temperature of personalized air, room temperature, clothing thermal insulation of the manikin, etc. Tracer gas was mixed with the room air. The air supplied by the SHPV was free of tracer gas. Tracer gas concentration in the air...


    Morikawa, Miki; Kanemitsu, Yoshitomi; Tsukamoto, Hiroki; Morikawa, Akimasa; Tomioka, Yoshihisa


    The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as β-lactoglobulin (β-LG) by Western blotting using specific monoclonal antibody and patient's sera. The β-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than β-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of β-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.

  8. Inhaled Beta2-agonist increases power output and glycolysis during sprinting in men

    DEFF Research Database (Denmark)

    Kalsen, Anders; Hostrup, Morten; Söderlund, Karin


    . Moreover, net rate of glycogenolysis (6.5±0.8 vs. 3.1±0.7 mmol glucosyl units kg dw s) and glycolysis (2.4±0.2 vs. 1.6±0.2 mmol glucosyl units kg dw s) were higher (P... and glycolysis in skeletal muscles. Furthermore, as terbutaline counteracted a reduction in ATP in type II fibers, terbutaline may postpone fatigue development in these fibers....

  9. Nanoparticle Inhalation Increases Microvascular Oxidative Stress and Compromises Nitric Oxide Bioavailability (United States)

    We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs are unclear. The purpose of this study was to identify alterations in the production of oxidative stress an...

  10. A hypothesis on the origin and evolution of the response to inhaled anesthetics


    Sonner, James M.


    An evolutionary narrative explaining why organisms respond to inhaled anesthetics is proposed. It is conjectured that organisms today respond to inhaled anesthetics because their ion channels are sensitive to inhaled anesthetics by virtue of common descent from ancestral, anesthetic-sensitive ion channels in one-celled organisms (i.e., that the response to anesthetics did not arise as an adaptation of the nervous system, but rather of ion channels that preceded the origin of multicellularity)...

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


    daily low-dose Bacillus anthracis spore inhalation exposures in the rabbit model Roy E. Barnewall 1, Jason E. Comer 1, Brian D. Miller 1, BradfordW...multiple exposure days. Keywords: Bacillus anthracis , inhalation exposures, low-dose, subchronic exposures, spores, anthrax, aerosol system INTRODUCTION... Bacillus Anthracis Spore Inhalation Exposures In The Rabbit Model 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  12. Treatment seeking behavior of inhalant using street children: Are we prepared to meet their treatment needs



    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/nongovernme...

  13. Labour time required for piglet castration with isoflurane-anaesthesia using shared and stationary inhaler devices. (United States)

    Weber, Sabrina; Das, Gürbüz; Waldmann, Karl-Heinz; Gauly, Matthias


    Isoflurane-anaesthesia combined with an analgesic represents a welfare-friendly method of pain mitigation for castration of piglets. However, it requires an inhaler device, which is uneconomic for small farms. Sharing a device among farms may be an economical option if the shared use does not increase labour time and the resulting costs. This study aimed to investigate the amount and components of labour time required for piglet castration with isoflurane anaesthesia performed with stationary and shared devices. Piglets (N = 1579) were anaesthetised with isoflurane (using either stationary or shared devices) and castrated.The stationary devices were used in a group (n = 5) of larger farms (84 sows/farm on an average), whereas smaller farms (n = 7; 32 sows/farm on an average) shared one device. Each farm was visited four times and labour time for each process-step was recorded. The complete process included machine set-up, anaesthesia and castration by a practitioner, and preparation, collection and transport of piglets by a farmer. Labour time of the complete process was increased (P = 0.012) on farms sharing a device (266 s/piglet) compared to farms using stationary devices (177 s/ piglet), due to increased time for preparation (P = 0.055), castration (P = 0.026) and packing (P = 0.010) when sharing a device. However, components of the time budget of farms using stationary or shared devices did not differ significantly (P > 0.05). Cost arising from time spent by farmers did not differ considerably between the use of stationary (0.28 Euro per piglet) and shared (0.26 Euro) devices. It is concluded that costs arising from the increased labour time due to sharing a device can be considered marginal, since the high expenses originating from purchasing an inhaler device are shared among several farms.

  14. Acute lung injury following inhalation exposure to nerve agent VX in guinea pigs. (United States)

    Wright, Benjamin S; Rezk, Peter E; Graham, Jacob R; Steele, Keith E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P


    A microinstillation technique of inhalation exposure was utilized to assess lung injury following chemical warfare nerve agent VX [methylphosphonothioic acid S-(2-[bis(1-methylethyl)amino]ethyl) O-ethyl ester] exposure in guinea pigs. Animals were anesthetized using Telazol-meditomidine, gently intubated, and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4 microg/m3, 70.4 micro g/m(m3), 90.4 microg/m(m3)) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 h of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 microg/m(m3) and 90.4 microg/m(m3) VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 microg/m(m3), indicating that this dose of VX caused lung injury that persisted at 24 h. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

  15. Assessment of the genotoxicity of trichloroethylene in the in vivo micronucleus assay by inhalation exposure. (United States)

    Wilmer, J W; Spencer, P J; Ball, N; Bus, J S


    The in vivo genotoxic potential of trichloroethylene (TCE) was evaluated by examining the incidence of micronucleated polychromatic erythrocytes (MN-PCEs) in the bone marrow. Groups of male CD rats were exposed by inhalation to targeted concentrations of 0 (negative control), 50, 500, 2500 or 5000 ppm for 6 consecutive hours on a single day. The exposure concentrations were selected to overlap those employed by a published study that reported a 2- to 3-fold increase in the frequency of micronuclei in male rats following a single inhalation exposure to 5, 500 and 5000 ppm TCE for 6h but not following repeated exposure to similar concentrations. In addition, any treatment-related findings were assessed in the context of potential TCE-induced hypothermia. Clinical signs consistent with marked TCE-induced sedation were observed in rats exposed to 5000 ppm and subsequently three rats died prior to the end of the 6h exposure period. No remarkable changes in body temperature were observed in surviving animals monitored with transponders before and after exposures. There were no statistically significant increases in the frequencies of MN-PCEs in groups treated with the test material as compared to the negative controls. The positive control animals showed a significant increase in the frequency of MN-PCEs and a decrease in the relative proportion of PCEs among erythrocytes as compared to the negative control animals. There were no statistically significant differences in the per cent PCEs in groups treated with the test material. As no increase in the incidence of micronuclei was observed in any of the TCE exposure groups, kinetochore analyses were not performed. Under the experimental conditions used, TCE was considered to be negative in the rat bone marrow micronucleus test.

  16. Opportunities for inhaler device selection in elderly patients with asthma or COPD

    Directory of Open Access Journals (Sweden)

    Barrons R


    Full Text Available Robert Barrons,1 James Wheeler,2 J Andrew Woods1 1Wingate University School of Pharmacy, Wingate, NC, USA; 2University of Tennessee Health Science Center, Nashville, TN, USA Abstract: An anticipated surge in the elderly population will be accompanied by a rise in aging patients with asthma or COPD. Clinician selection of inhalers needs to address the unique challenges to elderly patients. These challenges to the use of inhalers include diminished physical and cognitive abilities, as well as cost reimbursement issues associated with polypharmacy and the Medicare gap. Clinicians should consider patient preferences for an inhaler device that provides ease of administration, and addresses conveniences such as portability, visual, and auditory indicators of dosing completion. The addition of spacer devices resolves hand-breath coordination difficulty with pressurized metered dose inhalers, but reduces overall inhaler convenience. Soft mist inhalers (Respimat® improve ease of administration, but use may be limited by cost and formulary availability. Multiple dose dry powder inhalers provide convenience and simplified use by requiring only one to two steps prior to administration, but concerns of peak inspiratory flow requirements remain among patients with advanced age and severity of COPD. If unaddressed, these challenges to inhaler selection contribute to inappropriate use of inhalers in 41% to 69% of patients, accompanied by at least 51% non-adherence to treatment. Clinicians must first avail themselves of reputable educational resources regarding new inhaler developments and administration, for competent patient instruction. Patient education should include a checklist of inhaler technique, with physical demonstration of each device by the patient and provider. Device demonstration significantly improves inhaler technique and identifies the need for nebulization therapy. Clinician and patient knowledge of available inhalers and their

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

    Directory of Open Access Journals (Sweden)

    Paulo de Tarso Roth Dalcin


    Full Text Available 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 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.

  18. Effects of early intervention with inhaled sodium cromoglycate in childhood asthma. (United States)

    Yoshihara, S; Kanno, N; Yamada, Y; Ono, M; Fukuda, N; Numata, M; Abe, T; Arisaka, O


    International and Japanese guidelines classify childhood asthma as mild, moderate, or severe, and recommend treatment with "as needed" bronchodilators, inhaled sodium cromoglycate, and inhaled corticosteroids, respectively. Alternatively, some investigators proposed inhaled corticosteroids as first-line therapy to prevent airway inflammatory obstruction. This article describes a clinical study assessing the effect of early intervention with inhaled sodium cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic children treated with inhaled sodium cromoglycate for five years and whose age of onset of asthma was six year of age or younger. An end-of-study questionnaire completed the examination. Children administered oral or inhaled corticosteroids simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined by the Japanese Pediatric Allergic Committee, were reduced continuously during the five years after the start of sodium cromoglycate treatment. The frequency of emergency department visits and hospitalizations also decreased. Significant between-period intervention differences showed improvement of clinical outcomes for children with severe asthma during the five years of sodium cromoglycate inhalation. The early intervention regime of starting sodium cromoglycate inhalation within two years of the onset of asthma shows a large improvement in the long-term prognosis of childhood asthma, especially for children with severe asthma. It is possible that starting inhaled sodium cromoglycate earlier than the present recommendation of corticosteroids could further improve clinical outcomes, but a prospective study should be performed to verify our results.

  19. New dry powders for inhalation containing temozolomide-based nanomicelles for improved lung cancer therapy. (United States)

    Rosière, Rémi; Gelbcke, Michel; Mathieu, Véronique; Van Antwerpen, Pierre; Amighi, Karim; Wauthoz, Nathalie


    Besides the numerous advantages of a chemotherapy administered by the inhalation route for lung cancer therapy, dry powder for inhalation (DPI) offers many advantages compared to other techniques and seems to be a technique that is well-adapted to an anticancer treatment. DPI formulations were developed using the cytotoxic drug temozolomide and a new folate-grafted self-assembling copolymer, a conjugate of three components, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD). F-PEG-HMD was synthesized using carbodiimide-mediated coupling chemistry in three main steps. F-PEG-HMD was characterized by 1H-NMR, mass spectrometry and thermal analysis. F-PEG-HMD presented a critical micellar concentration in water of 4x10-7 M. F-PEG-HMD nanomicelles were characterized by a trimodal particle size distribution with Z-average diameter of 83±1 nm in water. Temozolomide-loaded nanomicelles were prepared by solubilization of F-PEG-HMD in the presence of temozolomide. Temozolomide solubility in water was increased in the presence of F-PEG-HMD (2-fold increase in molar solubility) which could potentially lead to increased local concentrations in the tumor site. The temozolomide-loaded F-PEG-HMD nanomicelles were characterized by a Z-average diameter of ~50 to ~60 nm, depending on the F-PEG-HMD concentration used. The nanomicelles were then spray-dried to produce dry powders. Temozolomide remained stable during all the formulation steps, confirmed by similar in vitro anticancer properties for the DPI formulations and a raw temozolomide solution. Two of the developed DPI formulations were characterized by good aerodynamic properties (with a fine particle fraction of up to 50%) and were able to release the F-PEG-HMD nanomicelles quickly in aqueous media. Moreover, in vitro, the two DPI formulations showed wide pulmonary deposition in the lower respiratory tract where adenocarcinomas are more often found. The present study, therefore, shows that F

  20. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yeon Soo [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Chung, Myung Hee [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)]. E-mail:; Park, Seog Hee [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Kim, Hyeon-Yeong [Industrial Chemicals Research Center, Industrial Safety and Health Research Institute KISCO, 104-8, Moonji-dong, Yusong-gu, Taejon-si 305-380 (Korea, Republic of); Choi, Byung Gil [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Lim, Hyun Wook [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Kim, Jin Ah [Department of Pathology, Holy Family Hospital, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon-si, Kyung gi-do 420-717 (Korea, Republic of); Yoo, Won Jong [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)


    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 {+-} 32.82 HU, 3 ppm: -720.65 {+-} 34.21 HU, 6 ppm: -756.41 {+-} 41.68 HU, 12 ppm: -812.56 {+-} 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow

  1. The toxicity of inhaled methanol vapors

    Energy Technology Data Exchange (ETDEWEB)

    Kavet, R.; Nauss, K.M. (Environmental Research Information, Inc., Palo Alto, CA (USA))


    Methanol could become a major automotive fuel in the U.S., and its use may result in increased exposure of the public to methanol vapor. Nearly all of the available information on methanol toxicity in humans relates to the consequences of acute, rather than chronic, exposures. Acute methanol toxicity evolves in a well-understood pattern and consists of an uncompensated metabolic acidosis with superimposed toxicity to the visual system. The toxic properties of methanol are rooted in the factors that govern both the conversion of methanol to formic acid and the subsequent metabolism of formate to carbon dioxide in the folate pathway. In short, the toxic syndrome sets in if formate generation continues at a rate that exceeds its rate of metabolism. Current evidence indicates that formate accumulation will not challenge the metabolic capacity of the folate pathway at the anticipated levels of exposure to automotive methanol vapor.117 references.

  2. Improving adherence with inhaler therapy in COPD

    Directory of Open Access Journals (Sweden)

    Suzanne C Lareau


    Full Text Available Suzanne C Lareau1, Barbara P Yawn21College of Nursing, University of Colorado Denver, Aurora, Colorado; 2Department of Research, Olmsted Medical Center, Rochester, Minnesota, USAAbstract: Chronic obstructive pulmonary disease (COPD is a major public health problem, associated with considerable morbidity and health care costs. The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies. Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes. But each of these strategies requires adherence. Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden. Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient. Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling. This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care.Keywords: chronic obstructive pulmonary disease, adherence, clinician

  3. Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice

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    Faller Simone


    Full Text Available Abstract Background Local pulmonary and systemic infections can lead to acute lung injury (ALI. The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury. Methods C57BL/6 N mice received lipopolysaccharide (LPS intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance. Results Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation. Conclusion Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses.

  4. Effects of inhaled L-arginine administration in a murine model of acute asthma.

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    Zeynep Arikan-Ayyildiz


    Full Text Available Increased arginase activity in the airways decreases L-arginine and causes deficiency of bronchodilating and anti-inflammatory nitric oxide (NO in asthma. As, it is suggested that L-arginine may have therapeutic potential in asthma treatment, we aimed to investigate the effects of inhaled L-arginine on oxygen saturation (SaO₂ and airway histology in a murine model of acute asthma. Twenty eight BALB/c mice were divided into four groups; I, II, III and IV (control. All groups except the control were sensitized and challenged with ovalbumin. After establishement of acute asthma attack by metacholine administration, the mice were treated with inhaled L-arginine (Group I, saline (Group II and budesonide (Group III, respectively. SaO₂was measured by pulse oximeter just before and 5 min after methacholine. A third measurement of SaO₂was also obtained 15 min after drug administration in these study groups. Inflammation in the lung tissues of the sacrificed animals were scored to determine the effects of the study drugs. The number of eosinophils in bronchoalveolar lavage (BAL was determined. The results indicated that inflammatory scores significantly improved in groups receiving study drugs when compared with placebo and L-arginine was similar in decreasing scores when compared with budesonide. SaO₂had a tendency to increase after L-arginine administration after acute asthma attack and this increase was statistically significant (p=0.043. Eosinophilia in BAL significantly reduced in group receiving L-arginine when compared with placebo (p<0.05. Thus in this study we demonstrated that L-arginine improved SaO₂and inflammatory scores in an acute model of asthma.

  5. Weaning of inhaled nitric oxide: is there a best strategy?

    Directory of Open Access Journals (Sweden)

    Anita M. Ware


    Full Text Available Background: Inhaled nitric oxide (iNO has been used in the treatment of pulmonary hypertension in neonates for many years. iNO was approved by the FDA in 1999 for hypoxic respiratory failure (HRF in term and near term infants, defined as > 34 weeks gestational age (GA. iNO is used for persistent pulmonary hypertension of the newborn (PPHN, secondary pulmonary hypertension caused by congenital heart disease (CHD, congenital diaphragmatic hernia (CDH, meconium aspiration syndrome (MAS, pneumonia, respiratory distress syndrome (RDS, and other pathologies. iNO has its effect locally on the pulmonary vasculature and has been studied extensively regarding its effect on morbidities such as: need for extracorporeal membrane oxygenation (ECMO, oxygen requirements, and mechanical ventilatory support. However, protocols for weaning iNO and for the duration of iNO weaning have not been studied extensively. It has been shown that an abrupt discontinuation leads to rebound pulmonary hypertension.Methods: Electronic literature search and review of published articles on the use of iNO in the neonate.Results: Electronic databases including Medline and PubMed were searched from the years 1995-2015, using the keywords "iNO", "nitric oxide", "neonate", and "weaning nitric oxide." This search revealed 2,124 articles. Articles were determined to be eligible for review if they included a specific protocol for weaning iNO, and were published in English. 16 articles with specific protocols for iNO weaning have been identified and reviewed. The studies had enrolled a total of 1,735 neonates either at term either preterm and with a mean birth weight of 3.3 kg (± 2 kg. Main diagnoses included MAS, CHD (total anomalous pulmonary venous return [TAPVR], d-transposition of the great vessels [DTGV], atrial septal defect [ASD], pulmonary atresia [PA], hypoplastic left heart syndrome [HLH], pneumonia, RDS, hyaline membrane disease (HMD, PPHN, CDH, sepsis, pulmonary hypoplasia

  6. Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis obliterans (United States)

    Calabrese, Cecilia; Corcione, Nadia; Rea, Gaetano; Stefanelli, Francesco; Meoli, Ilernando; Vatrella, Alessandro


    ABSTRACT Post-infectious bronchiolitis obliterans (PIBO) is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and followed for three years. After short- and long-term therapy with an inhaled corticosteroid/long-acting ß2 agonist combination, together with an inhaled long-acting antimuscarinic, the patient showed relevant improvement of airway obstruction that had been irreversible at the time of the bronchodilator test. The lung function of the patient worsened when he interrupted the triple inhaled therapy. In addition, a 3-week pulmonary rehabilitation program markedly improved his physical performance. PMID:27383939

  7. Impact of long-term treatment with inhaled corticosteroids and bronchodilators on lung function in a patient with post-infectious bronchiolitis obliterans

    Directory of Open Access Journals (Sweden)

    Cecilia Calabrese

    Full Text Available ABSTRACT Post-infectious bronchiolitis obliterans (PIBO is a small airways disease characterized by fixed airflow limitation. Therefore, inhaled bronchodilators and corticosteroids are not recommended as maintenance therapy options. The management of PIBO currently consists only of close monitoring of affected patients, aimed at the prevention and early treatment of pulmonary infections. In recent years, there has been an increase in the incidence of PIBO in the pediatric population. Patients with PIBO are characterized by a progressive decline in lung function, accompanied by a decrease in overall functional capacity. Here, we report the case of a relatively young man diagnosed with PIBO and followed for three years. After short- and long-term therapy with an inhaled corticosteroid/long-acting 2 agonist combination, together with an inhaled long-acting antimuscarinic, the patient showed relevant improvement of airway obstruction that had been irreversible at the time of the bronchodilator test. The lung function of the patient worsened when he interrupted the triple inhaled therapy. In addition, a 3-week pulmonary rehabilitation program markedly improved his physical performance.

  8. Beryllium contamination and exposure monitoring in an inhalation laboratory setting. (United States)

    Muller, Caroline; Audusseau, Séverine; Salehi, Fariba; Truchon, Ginette; Chevalier, Gaston; Mazer, Bruce; Kennedy, Greg; Zayed, Joseph


    Beryllium (Be) is used in several forms: pure metal, beryllium oxide, and as an alloy with copper, aluminum, or nickel. Beryllium oxide, beryllium metal, and beryllium alloys are the main forms present in the workplace, with inhalation being the primary route of exposure. Cases of workers with sensitization or chronic beryllium disease challenge the scientific community for a better understanding of Be toxicity. Therefore, a toxicological inhalation study using a murine model was performed in our laboratory in order to identify the toxic effects related to different particle sizes and chemical forms of Be. This article attempts to provide information regarding the relative effectiveness of the environmental monitoring and exposure protection program that was enacted to protect staff (students and researchers) in this controlled animal beryllium inhalation exposure experiment. This includes specific attention to particle migration control through intensive housekeeping and systematic airborne and surface monitoring. Results show that the protective measures applied during this research have been effective. The highest airborne Be concentration in the laboratory was less than one-tenth of the Quebec OEL (occupational exposure limit) of 0.15 microg/m(3). Considering the protection factor of 10(3) of the powered air-purifying respirator used in this research, the average exposure level would be 0.03 x 10(- 4) microg/m(3), which is extremely low. Moreover, with the exception of one value, all average Be concentrations on surfaces were below the Quebec Standard guideline level of 3 microg/100 cm(2) for Be contamination. Finally, all beryllium lymphocyte proliferation tests for the staff were not higher than controls.

  9. Inhaled Pharmacotherapy and Stroke Risk in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population Based Study Using Two-Stage Approach.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Lin

    Full Text Available Patients with chronic obstructive pulmonary disease (COPD are at higher risk of stroke than those without COPD. This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design.The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort. Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs, long-acting β-agonists (LABAs, and LABA plus inhaled corticosteroid (ICS, on the risk after adjustment for patient demographic characteristics and comorbid disorders.Of the 52,065 sampled patients, 2,689 (5.2% developed stroke during follow-up, including 727 (7.0% from the COPD cohort and 1,962 (4.7% from the comparison cohort (p < 0.001. Treatment with SABA was associated with 1.67-fold (95% CI 1.45-1.91; p < 0.001 increased risk of stroke in COPD patients. By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60-0.94, p = 0.014.Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction. Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD.

  10. Hospital washbasin water: risk of Legionella-contaminated aerosol inhalation. (United States)

    Cassier, P; Landelle, C; Reyrolle, M; Nicolle, M C; Slimani, S; Etienne, J; Vanhems, P; Jarraud, S


    The contamination of aerosols by washbasin water colonized by Legionella in a hospital was evaluated. Aerosol samples were collected by two impingement technologies. Legionella was never detected by culture in all the (aerosol) samples. However, 45% (18/40) of aerosol samples were positive for Legionella spp. by polymerase chain reaction, with measurable concentrations in 10% of samples (4/40). Moreover, immunoassay detected Legionella pneumophila serogroup 1 and L. anisa, and potentially viable bacteria were seen on viability testing. These data suggest that colonized hospital washbasins could represent risks of exposure to Legionella aerosol inhalation, especially by immunocompromised patients.

  11. Adrenal function in asthmatic children treated with inhaled budesonide

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Damkjaer Nielsen, M;


    The effect of the inhaled topical steroid budesonide on adrenal function was evaluated in 33 children (aged 7-15 years) with moderate bronchial asthma. The trial was designed as a prospective single-blind study of the effect of budesonide in daily doses of 200 microgram through 400 microgram to 800...... significantly during treatment with 800 microgram budesonide as compared to treatment with 200 microgram budesonide (95% confidence interval: 74%-112%). It is concluded, that budesonide is a topical steroid with a favourable ratio between topical and systemic effects in asthmatic children....

  12. Pneumomediastinum Secondary to Barotrauma after Recreational Nitrous Oxide Inhalation

    Directory of Open Access Journals (Sweden)

    H. Jeddy


    Full Text Available We present a case of a seventeen-year-old patient, admitted in the care of the surgical team following inhalation of nitrous oxide at high pressure, leading to extensive pneumomediastinum and surgical emphysema. We discuss the subsequent investigations and management for this patient. In the absence of history of airway injury and respiratory problems including asthma and with no oesophageal perforation on investigations, the diagnostic and management challenges encountered have been discussed which will help in future management of similar cases.

  13. Clearance of inhaled ceramic fibers from rat lungs.



    Deposition, clearance, retention, and durability of inhaled particles in lung are important factors for induction of pulmonary fibrosis or lung cancer. To study the deposition and clearance of aluminium silicate ceramic fibers from the lung, male Wistar rats were exposed to ceramic fibers, with a mass median aerodynamic diameter (MMAD) of 3.7 microns, for 6 hr/day, 5 days/week for 2 weeks. The average exposure concentration was 27.2 mg/m3 (SD 9.0). The rats were killed at 1 day, 1 month, 3 mo...

  14. Effect of inhaled drugs on anxiety and depression in patients with chronic obstructive pulmonary disease: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Hyun MK


    Full Text Available Min Kyung Hyun,1 Na Rae Lee,2 Eun Jin Jang,3 Jae-Joon Yim,4 Chang-Hoon Lee4 1Department of Preventive Medicine, College of Korean Medicine, Dongguk University, Gyeongju, Republic of Korea; 2National Evidence-based Healthcare Collaborating Agency, Seoul, Republic of Korea; 3Department of Information Statistics, College of Natural Science, Andong National University, Andong, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea Objective: We investigated the effect of treatment with inhaled drugs on changes in mood, focusing on depression and anxiety during treatment in patients with newly diagnosed chronic obstructive pulmonary disease (COPD.Methods: We prospectively selected new COPD patients from three Seoul National Hospitals. Participants underwent face-to-face interviews to evaluate clinical characteristics and drug use, and completed questionnaires using the Hospital Anxiety and Depression Scale (HADS at the start of the project, the 4th week, and the 12th week. We compared changes in HADS scores both between inhaled corticosteroid (ICS/long-acting β2 agonist (LABA users and non-ICS/LABA users, as well as between long-acting muscarinic antagonist (LAMA users and non-LAMA users. The general linear mixed model was applied for multivariate analysis.Results: Ninety new COPD patients participated in the study. Of these 90 patients, 84 completed face-to-face interviews. In the univariate analysis, those who were treated by ICS/LABA or LAMA showed a significant increase in HADS-A at the 4-week evaluation (0.73±2.56, P=0.038, but the statistical significance was lost in the multivariable analysis. No significant difference was found in the change in HADS scores between ICS/LABA users and non-ICS/LABA users, or between LAMA users and non-LAMA users in multivariate general linear mixed model

  15. Effect of outpatient therapy with inhaled corticosteroids on decreasing in-hospital mortality from pneumonia in patients with COPD

    Directory of Open Access Journals (Sweden)

    Yamauchi Y


    Full Text Available Yasuhiro Yamauchi,1 Hideo Yasunaga,2 Wakae Hasegawa,1 Yukiyo Sakamoto,1 Hideyuki Takeshima,1 Taisuke Jo,1,3 Hiroki Matsui,2 Kiyohide Fushimi,4 Takahide Nagase1 1Department of Respiratory Medicine, Graduate School of Medicine, 2Department of Clinical Epidemiology and Health Economics, School of Public Health, 3Division for Health Service Promotion, The University of Tokyo, 4Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan Background and objectives: Inhaled corticosteroids (ICS and long-acting inhaled bronchodilators (IBD are beneficial for the management of COPD. Although ICS has been reported to increase the risk of pneumonia in patients with COPD, it remains controversial whether it influences mortality. Using a Japanese national database, we examined the association between preadmission ICS therapy and in-hospital mortality from pneumonia in patients with COPD. Methods: We retrospectively collected data from 1,165 hospitals in Japan on patients with COPD who received outpatient inhalation therapy and were admitted with pneumonia. Patients were categorized into those who received ICS with IBD and those who received IBD alone. We performed multivariate logistic regression analysis to examine the association between outpatient ICS therapy and in-hospital mortality, adjusting for the patients’ backgrounds. Results: Of the 7,033 eligible patients, the IBD alone group (n=3,331 was more likely to be older, have lower body mass index, poorer general conditions, and more severe pneumonia than the ICS with IBD group (n=3,702. In-hospital mortality was 13.2% and 8.1% in the IBD alone and the ICS with IBD groups, respectively. After adjustment for patients’ backgrounds, the ICS with IBD group had significantly lower mortality than the IBD alone group (adjusted odds ratio, 0.80; 95% confidence interval, 0.68–0.94. Higher mortality was associated with older age, being male

  16. Oxidative stress markers in Thoroughbred horses after castration surgery under inhalation anesthesia. (United States)

    Tsuzuki, Nao; Sasaki, Naoki; Kusano, Kanichi; Endo, Yoshiro; Torisu, Shidow


    Oxidative stress has been reported to occur during surgery. It is important to reduce intraoperative oxidative stress to improve the postoperative prognosis. However, there are no reports regarding oxidative stress related to surgery in horses. In the present study, we measured pre and postsurgical diacron-reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP); the oxidative stress index (OSI) was then calculated (OSI=d-ROMs/BAP × 100). d-ROMs were not significantly different between the pre and postsurgical periods. However, BAP significantly decreased after surgery (P=0.02), and OSI significantly increased after surgery (P=0.02). Based on these results, it suggested that castration surgery under inhalation anesthesia decreases the antioxidant potential and causes oxidative stress in horses.

  17. Changes in body water distribution during treatment with inhaled steroid in pre-school children

    DEFF Research Database (Denmark)

    Heitmann, B L; Anhøj, Jacob; Bisgaard, A M;


    .i.d. delivered via Babyhaler, budesonide pressurized metered dose inhaler (pMDI) 200 microg b.i.d. delivered via Nebuchamber and placebo. Spacers were primed before use. In total, 40 children aged 1-3 years, with mild intermittent asthma were included. Twenty-five of the children completed all three treatments....... At the end of each treatment period body impedance and skin ultrasonography were measured. METHODS AND PROCEDURES: We measured changes in water content of the soft tissues by two methods. Skin ultrasonography was used to detect small changes in dermal water content, and bioelectrical impedance was used...... to assess body water content and distribution. MAIN OUTCOMES AND RESULTS: We found an increase in skin density of the shin from fluticasone as measured by ultrasonography (p = 0.01). There was a tendency for a consistent elevation of impedance parameters from active treatments compared to placebo although...

  18. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe

    DEFF Research Database (Denmark)

    Burbach, G J; Heinzerling, L M; Edenharter, G


    the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. METHODS: Clinical relevance of skin prick tests was recorded with regard to patient history...... the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.......BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance...

  19. Appropriate use of inhaled corticosteroids in COPD: the candidates for safe withdrawal (United States)

    Yawn, Barbara P; Suissa, Samy; Rossi, Andrea


    International guidance on chronic obstructive pulmonary disease (COPD) management recommends the use of inhaled corticosteroids (ICS) in those patients at increased likelihood of exacerbation. In spite of this guidance, ICS are prescribed in a large number of patients who are unlikely to benefit. Given the evidence of the risks associated with ICS and the limited indications for their use, there is interest in understanding the effects of withdrawing ICS when prescribed inappropriately. In this review, we discuss the findings of large ICS withdrawal trials, with primary focus on the more recent trials using active comparators. Data from these trials indicate that ICS may be withdrawn without adverse impact on exacerbation risk and patient-reported outcomes in patients with moderate COPD and no history of frequent exacerbations. Considering the safety concerns associated with ICS use, these medications should be withdrawn in patients for whom they are not recommended, while maintaining adequate bronchodilator therapy. PMID:27684954

  20. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids

    DEFF Research Database (Denmark)

    Watz, Henrik; Tetzlaff, Kay; Wouters, Emiel F M


    BACKGROUND: Blood eosinophil counts might predict response to inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. We used data from the WISDOM trial to assess whether patients with COPD with higher blood eosinophil counts would...... to receive either continued or reduced ICS over 12 weeks. We did a post-hoc analysis after complete ICS withdrawal (months 3-12) to compare rate of exacerbations and time to exacerbation outcomes on the basis of blood eosinophil subgroups of increasing cutoff levels. The WISDOM trial is registered...... at, number NCT00975195. FINDINGS: In the 2296 patients receiving treatment after ICS withdrawal, moderate or severe exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts (out of total white blood cell count) of 2...

  1. Numerical Modelling of Agglomeration and Deagglomeration in Dry Powder Inhalers: A Review. (United States)

    Yang, Jiecheng; Wu, Chuan-Yu; Adams, Michael


    Numerical modelling using computational fluid mechanics (CFD) and discrete element method (DEM) becomes increasingly prevalent for the exploration of agglomeration and deagglomeration in dry powder inhalers (DPIs). These techniques provide detailed information on air flow and particle-particle/wall interaction, respectively. Coupling of CFD and DEM enables an in-depth investigation of the mechanisms at the microscopic level. This paper reviews the applications of CFD and DEM in DPI development and optimisation. The recent progress in modelling of two key processes in DPIs, i.e. agglomeration and deagglomeration, is presented. It has been demonstrated that DEM-CFD is a promising numerical approach to investigate the underlying agglomeration and deagglomeration mechanisms for DPIs. With further advances in computing capacity, it is expected that DEM-CFD will be capable of addressing more realistic and complicated issues in DPI improvement.

  2. Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine

    Institute of Scientific and Technical Information of China (English)

    Lei Xiang; Jing-Wang Tan; Li-Jie Huang; Lin Jia; Ya-Qian Liu; Yu-Qiong Zhao; Kai Wang; Jia-Hong Dong


    AIM:To study the effect of H2 gas on liver injury in massive hepatectomy using the Intermittent Pringle maneuver in swine.METHODS:Male Bama pigs (n =14) treated with ketamine hydrochloride and Sumianxin Ⅱ as induction drugs followed by inhalation anesthesia with 2% isoflurane,underwent 70% hepatotectomy with loss of bleeding less than 50 mL,and with hepatic pedicle occlusion for 20 min,were divided into two groups:Hydrogen-group (n =7),the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; Contrast-group (n =7),underwent 70% hepatotectomy without inhalation of hydrogen.Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT),aspartate aminotransferase (AST),hyaluronic acid (HA),tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),and malondialdehyde (MDA) in liver tissue were measured at pre-operation,post-hepatotectomy (PH) 1 h and 3 h.The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h.Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine.RESULTS:There were no significant differences in body weight,blood loss and removal liver weight between the two groups.There was no significant difference in changes of portal vein pressure between two groups at pre-operation,PH 30 min,but in hydrogen gas treated-group it slightly decrease and lower than its in Contrast-group at PH 3 h,although there were no significant difference (P =0.655).ALT and AST in Hydrogen-group was significantly lower comparing to Contrast-group (P =0.036,P =0.011,vs P =0.032,P =0.013) at PH 1 h and 3 h,although the two groups all increased.The MDA level increased between the two group at PH 1 h and 3 h.In the hydrogen gas treated-group,the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to

  3. Comparative evaluation of the effects of short-term inhalation exposure to diesel engine exhaust on rat lung and brain

    Energy Technology Data Exchange (ETDEWEB)

    Berlo, Damien van; Albrecht, Catrin; Krutmann, Jean; Schins, Roel P.F. [Institut fuer Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universitaet Duesseldorf GmbH, Duesseldorf (Germany); Knaapen, Ad M.; Schooten, Frederik-Jan van [Maastricht University, Department of Health Risk Analysis and Toxicology, Maastricht (Netherlands); Cassee, Flemming R.; Gerlofs-Nijland, Miriam E.; Kooter, Ingeborg M. [National Institute for Public Health and the Environment (RIVM), Centre for Environmental Health, Bilthoven (Netherlands); Palomero-Gallagher, Nicola [Research Center Juelich, Institute of Neurosciences and Medicine (INM-2), Juelich (Germany); Bidmon, Hans-Juergen [Heinrich-Heine-University, C and O Vogt Institute for Brain Research, Duesseldorf (Germany)


    Combustion-derived nanoparticles, such as diesel engine exhaust particles, have been implicated in the adverse health effects of particulate air pollution. Recent studies suggest that inhaled nanoparticles may also reach and/or affect the brain. The aim of our study was to comparatively evaluate the effects of short-term diesel engine exhaust (DEE) inhalation exposure on rat brain and lung. After 4 or 18 h recovery from a 2 h nose-only exposure to DEE (1.9 mg/m{sup 3}), the mRNA expressions of heme oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and cytochrome P450 1A1 (CYP1A1) were investigated in lung as well as in pituitary gland, hypothalamus, olfactory bulb, olfactory tubercles, cerebral cortex, and cerebellum. HO-1 protein expression in brain was investigated by immunohistochemistry and ELISA. In the lung, 4 h post-exposure, CYP1A1 and iNOS mRNA levels were increased, while 18 h post-exposure HO-1 was increased. In the pituitary at 4 h post-exposure, both CYP1A1 and HO-1 were increased; HO-1 was also elevated in the olfactory tuberculum at this time point. At 18 h post-exposure, increased expression of HO-1 and COX-2 was observed in cerebral cortex and cerebellum, respectively. Induction of HO-1 protein was not observed after DEE exposure. Bronchoalveolar lavage analysis of inflammatory cell influx, TNF-{alpha}, and IL-6 indicated that the mRNA expression changes occurred in the absence of lung inflammation. Our study shows that a single, short-term inhalation exposure to DEE triggers region-specific gene expression changes in rat brain to an extent comparable to those observed in the lung. (orig.)

  4. Predictive models for deposition of inhaled diesel exhaust particles in humans and laboratory species

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C.P.; Xu, G.B. (State Univ. of New York at Buffalo, Amherst (USA))


    Mathematical and computer models of the respiratory tracts of human beings and of laboratory animals (rats, hamsters, guinea pigs) were used to estimate the deposition patterns of inhaled diesel exhaust particles from automobile emissions. Our goal was to be able to predict the relation between exposure to diesel exhaust particles and the deposition of these particles in the lungs of humans of various ages. Diesel exhaust particles are aggregates with a mass median aerodynamic diameter of approximately 0.2 micron. Their actual size depends on the conditions under which they are generated. Using an appropriate particle model, we derived mathematical expressions that describe the effects of diffusion, sedimentation, impaction, and interception on the deposition of these particles. Because of their small size, we found that most diesel exhaust particles deposited through diffusion, and that the role of the other mechanisms was minor. Anatomical models of the human lung from birth to adulthood, as well as models of the lungs of laboratory species were formulated mathematically using available morphometric data. We used these lung models, together with the corresponding ventilation conditions of each species, to calculate deposition of diesel exhaust particles in the lungs. Under normal breathing conditions, we calculated that 7 to 13 percent (depending on particle size) of inhaled diesel exhaust particles deposit in the alveolar region of the adult human lung. Although the breathing mode (nose or mouth breathing) did not appear to affect alveolar deposition, increasing the minute ventilation increased alveolar deposition significantly. The calculated deposition patterns for diesel exhaust particles in younger humans (under age 25) were similar.

  5. Prenatal Inhalation Exposure to Evaporative Condensates of Gasoline with 15% Ethanol and Evaluation of Sensory Function in Adult Rat Offspring (United States)

    The introduction of ethanol-blended automotive fuels has raised concerns about potential health effects from inhalation exposure to the combination of ethanol and gasoline hydrocarbon vapors. Previously, we evaluated effects of prenatal inhalation exposure to 100% ethanol (E100) ...

  6. 吸入性损伤的研究进展%Advancement in study of inhalation injury

    Institute of Scientific and Technical Information of China (English)



    Inhalation injury is a major contributor to the morbidity and mortality associated with serious burns. The improvement in the understanding of smoke inhalation injury had been obtained in the last half century in China. The models of steam and smoke inhalation injury had been reproduced and a series of experimental studies had been performed .It was found that chemical bronchotracheitis, pulmonary edema and alveolar collapse(atelectasis) were the primary pathologic findings after inhalation injury. The second inflammatory response would play an important role in the development of acute respiratory failure. The roles of some cytokines, inflammatory cells and pulmonary surfactants in the development of inhalation injury had been elucidated. The etologic factors and the pathophysiologic changes in inhalation injury had been illustrated clearly. These basic science investigations had led to the advances in protective strategies for the complications of inhalation injury. Now the morbidity and mortality of inhalation injury have decreased markedly in China.

  7. Use of pressurised aerosol inhalers among patients attending the Chest Clinic and Primary Care Department of University Hospital, Kuala Lumpur. (United States)

    Liam, C K; Lo, Y L; Yap, B H; Low, S H; Ariwalagam, M


    Eighty consecutive patients who came to collect their prescriptions for pressurised aerosol inhalers at the Pharmacy of the University Hospital, Kuala Lumpur, were interviewed regarding their use of the pressurised inhaler. Their inhaler technique was also assessed. A significant proportion inhaled the steroid aerosol before the bronchodilator and 23.5% used the steroid inhaler for relief of acute dyspnoea. Only 28.8% of the 80 patients performed correctly all 6 steps necessary for the proper use of inhalers. The most common mistake was the failure to inhale slowly and deeply. Patients who had used the device for more than 5 years performed better, while correct inhaler technique was not dependent on the patient's sex, age or level of education.

  8. Análise da redistribuição de calor com agentes inalatórios, em ratos submetidos a laparotomia e pneumoperitônio, através da termografia infravermelha Análisis de la redistribución de calor con agentes inhalatorios, en ratones sometidos a laparotomia y pneumoperitonio, a través de termografia infraroja Analysis of heat loss using inhalation agents in rats subjected to laparotomy and increased intra-abdominal pressure, using digital infrared thermal image

    Directory of Open Access Journals (Sweden)

    Daniel Colman


    , distribuidos en tres grupos, en que fueron utilizados: halotano, isoflurano y sevoflurano. En cada grupo hubo división en otros tres sub-grupos: I - control, II - laparotomia mediana con exposición de alzas intestinales; III - pneumoperitonio de 15 mmHg. La análisis termodinámica se realizó de dos formas: a través de la temperatura central esofágica y de la imagen digital térmica infrarroja. RESULTADOS: No hubo diferencia significativa en relación a los anestésicos inhalatorios entre los grupos I y II en relación a la pérdida de calor. En relación al grupo III, hubo diferencia entre el isoflurano y el sevoflurano, siendo el isoflurano el anestésico responsable por la mayor pérdida de temperatura en el animal. CONCLUSIONES: El sevoflurano fue el agente anestésico inhalatorio que determinó menor pérdida de calor frente al pneumoperitonio, en relación al isoflurano y halotano.BACKGROUND AND OBJECTIVES: Anesthesiology involves the handling of situations inherent to anesthetic and surgical procedures which lead to patients thermal homeostasis unbalance, with noxious physiological effects. This study aimed at qualifying and quantifying thermal redistribution in rats subjected to inhalation anesthesia, during induction and in surgical situations of laparotomy and increased intra-abdominal pressure. METHODS: The study involved 90 rats, submitted to inhalation anesthesia, which were distributed in three groups: halothane; isoflurane; sevoflurane. Each group was divided in subgroups: I - control; II - median laparotomy with bowel exposure; III - 15 mmHg Increase in intra-abdominal pressure. Heat loss was measured by an esophageal probe and infrared thermal image. RESULTS: There were no significant differences among inhalation anesthetics regarding heat loss between groups I and II. In group III, there was a difference between isoflurane and sevoflurane and isoflurane was responsible for the highest heat loss.

  9. Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

    Institute of Scientific and Technical Information of China (English)

    Qiujun WANG; Kezhong LI; Shanglong YAO


    Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromo-cytoma cells (PC12) in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endo-plasmic reticulum (ER) via activation of inositol 1,4,5-trisphosphate (IP3) receptors. Alzheimer's pre-senilin-1 (PS1) mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intraceUular calcium homeostasis and thus being less potent to cause cytotoxicity. This study examined and com- pared the cytotoxic effects of various inhaled anesthetics on PC12 cells transfected with the Alz- heimer's mutated Psi (L286V) and the disruption of intracellular calcium homeostasis. PC12 cells transfected with wild type (WT) and mutated PS1 (L286V) were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were per- formed to evaluate cell viability. Changes of calcium concentration in cytosolic space ([Ca2+]c) were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca2+]c in L286V than in the WT cells. Xestospongin C significantly amelio- rated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca2+]c in L286V PC12 cells. These results suggested that isoflurane induced cytoxicity by

  10. Inhalation anesthesia in dumeril´s monitor with isofluane, sevofluane, and nitrus oxide

    DEFF Research Database (Denmark)

    Bertelsen, Mads Frost; Mosley, Craig; Crawshaw, Graham J.


    Induction and recovery from inhalation anesthesia of Dumeril´s monitors using isoflurane, sevoflurane and nitrus oxide were characterized using a randomized crossover design.......Induction and recovery from inhalation anesthesia of Dumeril´s monitors using isoflurane, sevoflurane and nitrus oxide were characterized using a randomized crossover design....

  11. A pooled analysis of FEV1, decline in COPD patients randomized to inhaled corticosteroids or placebo

    NARCIS (Netherlands)

    Soriano, Joan B.; Sin, Don D.; Zhang, Xuekui; Camp, Pat G.; Anderson, Julie A.; Anthonisen, Nick R.; Buist, A. Sonia; Burge, P. Sherwood; Calverley, Peter M.; Connett, John E.; Petersson, Stefan; Postma, Dirkje S.; Szafranski, Wojciech; Vestbo, Jorgen


    Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven l

  12. The impact of large tidal volume ventilation on the absorption of inhaled insulin in rabbits

    DEFF Research Database (Denmark)

    Petersen, Astrid Heide; Laursen, Torben; Ahrén, Bo;


    Previous studies have shown that ventilation patterns affect absorption of inhaled compounds. Thus, the aim of this study was to investigate the effect of large tidal volume ventilation (LTVV) on the absorption of inhaled insulin in rabbits. Mechanically ventilated rabbits were given human insuli...

  13. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO) : a randomised controlled trial

    NARCIS (Netherlands)

    Mercier, Jean-Christophe; Hummler, Helmut; Durrmeyer, Xavier; Sanchez-Luna, Manuel; Carnielli, Virgilio; Field, David; Greenough, Anne; Van Overmeire, Bart; Jonsson, Baldvin; Hallman, Mikko; Baldassarre, James


    Background In animal models, inhaled nitric oxide improved gas exchange and lung structural development, but its use in premature infants at risk of developing bronchopulmonary dysplasia remains controversial. We therefore tested the hypothesis that inhaled nitric oxide at a low concentration, start

  14. [Age-related characteristics of inhalant abuse in adolescents with conduct disorders]. (United States)

    Grechanyĭ, S V; Egorov, A Iu


    Objective. The aim of the study was to determine the relation between inhalant abuse and conduct disorders in adolescents. Material and methods. Authors studied 95 adolescents with ICD-10 diagnoses conduct disorders (F91.1, 91.2), "Mental and behavioral disorders due to use of inhalant abuse. Harmful use" (F18.1) and "Inhalant drug dependence" (F18.2). "The Nisonger Child Behavior Rating Form" ("NCBRF, TIQ version") and "Adolescent Drug Abuse Diagnosis (ADAD)" ("EvroADAD" version) were used. Two teenager groups were investigated: the younger (mean age 14.35±0.844 years) one and the older (mean age 16.30±0.464 years) ones. Clinical manifestations of inhalant intoxication and symptoms of addiction were described. Using cluster analysis, the relation of clinical manifestations of conduct disorder with symptoms of inhalant addiction and its consequences were calculated. Results and conclusion. In the younger group, no significant statistical relationships were found. In the older group, 3 cluster were detected: 1) the variables that characterized the relationship of inhalant abuse with typical behavioral patterns such as delinquency, school and social maladjustment; 2) the variables that characterized the transformation of the inhalant use to alcohol use which was associated with hyperkinetic conduct disorder; 3) the variables that characterize a pronounced health and psychological consequences of the inhalant use.

  15. Inhaled corticosteroids should be the first line of treatment for children with asthma

    NARCIS (Netherlands)

    Brand, Paul L. P.


    Although montelukast is claimed to be preferable to inhaled corticosteroids in children with asthma and allergic rhinitis, virus-induced exacerbations, exercise induced asthma, and in those experiencing difficulties with inhalation therapy, there is no scientific evidence to support any of these cla

  16. Reversibility after inhaling salbutamol in different body postures in asthmatic children: a pilot study

    NARCIS (Netherlands)

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


    Rationale Pulmonary medication is mostly delivered in the form of medical aerosols to minimize systemic side effects. A major drawback of inhaled medication is that the majority of inhaled particles impacts in the oropharynx at the sharp bend of the airway. Stretching the airway by a forward leaning

  17. Retail sales of inhalation devices in European countries: so much for a global policy.

    NARCIS (Netherlands)

    Lavorini, F.; Corrigan, C.J.; Barnes, P.J.; Dekhuijzen, P.N.R.; Levy, M.L.; Pedersen, S.; Roche, N.; Vincken, W.; Crompton, G.K.


    OBJECTIVE: To evaluate the retail sales of pressurised metered-dose inhalers (pMDIs), dry-powder inhalers (DPIs) and liquids for nebulisation in 16 European countries. METHODS: Retail sales data relating to pMDIs, DPIs and liquids for nebulisation delivering short- and long-acting bronchodilators, c

  18. Comparative in vitro performance of the new drug aclidinium in a novel multidose dry powder inhaler

    NARCIS (Netherlands)

    Gjaltema, Doetie; Hagedoorn, Paul; Grasmeijer, Floris; Huijbers, Bernardus G.; Frijlink, Henderik W.; De Boer, Anne H.


    Background: With new inhalation products, lack of knowledge of how much drug is deposited at the site of action in the lungs plus variation in performance of inhalation devices can lead to inaccurate conclusions about drug efficacy. Aim: To compare the consistency of delivered dose (DD) and fine par

  19. The pharmacokinetic profile of inhaled and oral salbutamol in elite athletes with asthma and nonasthmatic subjects

    DEFF Research Database (Denmark)

    Elers, Jimmi; Pedersen, Lars; Henninge, John;


    Data on pharmacokinetics of inhaled and oral salbutamol in elite athletes with asthma are needed to differentiate between therapeutic use and doping in doping control.......Data on pharmacokinetics of inhaled and oral salbutamol in elite athletes with asthma are needed to differentiate between therapeutic use and doping in doping control....

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

    NARCIS (Netherlands)

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


    Rationale Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by

  1. An investigation into the predictive value of cascade impactor results for side effects of inhaled salbutamol

    NARCIS (Netherlands)

    Weda, M; Zanen, P; de Boer, A H; Barends, D M; Frijlink, H W


    The aim of this study was to compare the Multistage Liquid Impinger (MSLI) and the Andersen Cascade Impactor (ACI) with respect to their power to predict differences in side effects of salbutamol delivered by a dry powder inhaler. Three preparations with the same nominal dose and the same inhaler de

  2. In Vivo Performance Testing of the Novel Medspray (R) Wet Aerosol Inhaler

    NARCIS (Netherlands)

    Munnik, P.; Boer, de A.H.; Wissink, J.; Hagedoorn, P.; Heskamp, I.; Kruijf, de W.; Rijn, van C.J.M.; Frijlink, H.W.; Zanen, P.


    Background: Monodisperse salbutamol inhalers were compared to select the optimal mass median aerodynamic diameter: 4.0, 5.0 or 6.0 mu m. Methods: Fifteen mild asthmatic patients participated. In all a FEV1-response of >12% (vs. baseline) or >200 mL after inhalation of 200 mu g salbutamol was m


    As part of a project to inform approaches for risk assessment of inhaled irritants of interest to homeland security, a set of acute (Peay et aI., SOT 2010) and subacute (George et aI., SOT 2010) studies of inhaled chlorine (CI2) in female F344 rats was performed. The exposure des...

  4. Investigation of the applicability of dry powder inhalation in school children

    NARCIS (Netherlands)

    Lexmond, A. J.; Kruizinga, T. J.; Hagedoorn, P.; Frijlink, H. W.; Rottier, B. L.; de Boer, A. H.


    Children are an important target group for inhalation therapy, but little is known about their intellectual and inspiratory capacities to operate dry powder inhalers (DPIs). Most studies so far have focused either on a specific DPI, or on (single) inhala- tion parameters and how these are affected b

  5. [Technology of nitrous oxide/oxygen inhalation sedation and its clinical application in pediatric dentistry]. (United States)

    Zhong, Tian; Hu, Daoyong


    Dental fear is a common problem in pediatric dentistry. Therefore, sedation for pediatric patients is an essential tool for anxiety management. Nitrous oxide/oxygen inhalation sedation is a safe, convenient, effective way to calm children. The review is about the technology of nitrous oxide/oxygen inhalation sedation and its clinical application in pediatric dentistry.

  6. Inhalant and Prescription Medication Abuse among Adolescents: An Inexpensive, Accessible, and Misperceived Trend (United States)

    Sikes, April; Walley, Cynthia; McBride, Rebecca; Fusco, Angela; Cole, Rebekah F.; Lauka, Justin


    Inhalant and prescription medication abuse, particularly among adolescents, are serious problems in our society. Several risk factors associated with inhalant and medication abuse among adolescents have been identified. As a result, adolescents may suffer multiple consequences in a range of developmental areas. The purpose of this article is to…

  7. Effects of tumors on inhaled pharmacologic drugs: I. Flow patterns. (United States)

    Martonen, T B; Guan, X


    Lung carcinomas are now the most common form of cancer. Clinical data suggest that tumors are found preferentially in upper airways, perhaps specifically at carina within bifurcations. The disease can be treated by aerosolized pharmacologic drugs. To enhance their efficacies site-specific drugs must be deposited selectively. Since inhaled particles are transported by air, flow patterns will naturally affect their trajectories. Therefore, in Part I of a systematic investigation, we focused on tumor-induced effects on airstreams, in Part II (the following article [p. 245]), particle trajectories were determined. To facilitate the targeted delivery of inhaled drugs, we simulated bifurcations with tumors on carinas using a commercial computational fluid dynamics (CFD) software package (FIDAP) with a Cray T90 supercomputer and studied effects of tumor sizes and ventilatory parameters on localized flow patterns. Critical tumor sizes existed; e.g., tumors had dominant effects when r/R > or = 0.8 for bifurcation 3-4 and r/R > or = 0.6 for bifurcation 7-8 (r = tumor radius and R = airway radius). The findings suggest that computer modeling is a means to integrate alterations to airway structures caused by diseases into aerosol therapy protocols.

  8. Assessment of bioaerosols and inhalable dust exposure in Swiss sawmills. (United States)

    Oppliger, Anne; Rusca, Sophie; Charrière, Nicole; Vu Duc, Trinh; Droz, Pierre-Olivier


    An assessment of wood workers' exposure to airborne cultivable bacteria, fungi, inhalable endotoxins and inhalable organic dust was performed at 12 sawmills that process mainly coniferous wood species. In each plant, samples were collected at four or five different work sites (debarking, sawing, sorting, planing and sawing cockpit) and the efficiency of sampling devices (impinger or filter) for determining endotoxins levels was evaluated. Results show that fungi are present in very high concentrations (up to 35 000 CFU m(-3)) in all sawmills. We also find that there are more bioaerosols at the sorting work site (mean +/- SD: 7723 +/- 9919 CFU m(-3) for total bacteria, 614 +/- 902 CFU m(-3) for Gram-negative, 19 438 +/- 14 246 CFU m(-3) for fungi, 7.0 +/- 9.0 EU m(-3) for endotoxin and 2.9 +/- 4.8 g m(-3) for dust) than at the sawing station (mean +/- SD: 1938 +/- 2478 CFU m(-3) for total bacteria, 141 +/- 206 CFU m(-3) for Gram-negative, 12 207 +/- 10 008 CFU m(-3) for fungi, 2.1 +/- 1.9 EU m(-3) for endotoxin and 0.75 +/- 0.49 mg m(-3) for dust). At the same time, the species composition and concentration of airborne Gram-negative bacteria were studied. Penicillinium sp. were the predominant fungi, while Bacillus sp. and the Pseudomonadacea family were the predominant Gram-positive and Gram-negative bacteria encountered, respectively.

  9. Urine concentrations of repetitive doses of inhaled salbutamol

    DEFF Research Database (Denmark)

    Elers, J; Pedersen, Lars; Henninge, J


    We examined blood and urine concentrations of repetitive doses of inhaled salbutamol in relation to the existing cut-off value used in routine doping control. We compared the concentrations in asthmatics with regular use of beta2-agonists prior to study and healthy controls with no previous use...... of beta2-agonists. We enrolled 10 asthmatics and 10 controls in an open-label study in which subjects inhaled repetitive doses of 400 microgram salbutamol every second hour (total 1600 microgram), which is the permitted daily dose by the World Anti-Doping Agency (WADA). Blood samples were collected...... and the median ranged from 268 to 611 ng×mL (-1). No samples exceeded the WADA threshold value of 1000 ng×mL (-1) when corrected for the urine specific gravity. When not corrected one sample exceeded the cut-off value with urine concentration of 1082 ng×mL (-1). In conclusion we found no differences in blood...

  10. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy. (United States)

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B H


    Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa.

  11. Development of liposomal salbutamol sulfate dry powder inhaler formulation. (United States)

    Huang, Wen-Hua; Yang, Zhi-Jun; Wu, Heng; Wong, Yuen-Fan; Zhao, Zhong-Zhen; Liu, Liang


    The purpose of our study was to develop a formulation of liposomal salbutamol sulfate (SBS) dry powder inhaler (DPI) for the treatment of asthma. Liposomes of high encapsulation efficiency (more than 80%) were prepared by a vesicular phospholipid gel (VPG) technique. SBS VPG liposomes were subjected to lyophilization using different kinds of cryoprotectants in various mass ratios. Coarse lactose (63-106 microm) in different mass ratios was used as a carrier. Magnesium stearate (0.5%) was added as a lubricator. The dry liposomal powders were then crushed by ball milling and sieved through a 400-mesh sieve to control the mean particle size at about 10 microm. The effects of different kinds of cryoprotectants and the amount of lactose carrier on the fine particle fraction (FPF) of SBS were investigated. The results showed that the developed formulation of liposomal dry powder inhaler was obtained using lactose as a cryoprotectant with a mass ratio of lyophilized powder to carrier lactose at 1 : 5; 0.5% magnesium stearate was used as a lubricator. The value of FPF for SBS was 41.51+/-2.22% for this formulation. Sustained release of SBS from the VPG liposomes was found in the in vitro release study. The study results offer the promising possibility of localized pulmonary liposomal SBS delivery in the anhydrous state.

  12. Inhaled iloprost for the treatment of pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    H. Olschewski


    Full Text Available Prostacyclin and its analogues (prostanoids are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience. Intravenous and subcutaneous prostanoids have clearly demonstrated efficacy in severe PAH, but adverse events related to the drug delivery system, systemic side-effects and tachyphylaxis have driven research into alternative prostanoid treatments. Iloprost is administered by inhalation, and thus avoids most of the systemic side-effects associated with i.v. or subcutaneous prostanoid infusion. Two randomised controlled 12-week trials in patients with PAH have demonstrated efficacy and a favourable safety profile for iloprost as monotherapy (the AIR trial and in combination with oral bosentan (STEP. Open-label uncontrolled long-term studies of inhaled iloprost therapy indicate that this treatment may improve long-term outcomes in PAH.

  13. Heavy metal in inhalable and respirable particles in urban atmosphere

    Directory of Open Access Journals (Sweden)

    T.F. Ediagbonya


    Full Text Available Human activities in Sapele are veritable sources of particulate pollution which are exuded into the atmosphere. These activities include bush burning which is one of the pre-planting activities, transportation, gas flaring, incineration of wastes refuse disposal and the use of wood as a source of fuel. The objective of this study is to determine the concentration of the trace metal in particulate matter captured in glass fibre filter paper. High volume sampler was used to collect the respirable and inhalable suspended particulate matter at ten different sites located in Sapele, from December 2010 to April 2011. The foam and the glass fibre filter were analysed for nine (Mn, Ni, Cr, Cd, Zn, Cu, Co, Fe, and Pb respectively by Flame Atomic Absorption Spectrophotometer (FAAS. The concentration of the respirable particle ranged from 104.17 to 145.83ug/cubic meter while the inhalable concentration ranged from 166.67 to 812.50ug/cubic meter. From the analysis the element Cd was moderately enriched.

  14. Deposition of inhaled wood dust in the nasal cavity. (United States)

    Tian, Z F; Inthavong, K; Tu, J Y


    Detailed deposition patterns of inhaled wood dust in an anatomically accurate nasal cavity were investigated using computational fluid dynamics (CFD) techniques. Three wood dusts, pine dust, heavy oak dust, and light oak dust, with a particle size distribution generated by machining (Chung et al., 2000), were simulated at an inhalation flow rate of 10 L/min. It was found that the major particle deposition sites were the nasal valve region and anterior section of the middle turbinate. Wood dust depositing in these regions is physiologically removed much more slowly than in other regions. This leads to the surrounding layer of soft tissues being damaged by the deposited particles during continuous exposure to wood dust. Additionally, it was found that pine dust had a higher deposition efficiency in the nasal cavity than the two oak dusts, due to the fact that it comprises a higher proportion of larger sized particles. Therefore, this indicates that dusts with a large amount of fine particles, such as those generated by sanding, may penetrate the nasal cavity and travel further into the lung.

  15. Inhaled loxapine: A novel treatment for agitation in psychotic disorders

    Directory of Open Access Journals (Sweden)

    Siwek, Marcin


    Full Text Available Psychomotor agitation is a widespread clinical problem both in patients with schizophrenia and BD. It is a highly hazardous condition, imposing significant risks in psychiatric emergency, as expressed by elevated ratios of adverse events and traumatic experiences (both for patients and medical staff. The available anti-agitation drugs have numerous disadvantages. The orally administered medications (even though preferable to patients take hours or even days for the therapeutic effect to emerge (and also there is a risk of exacerbating agitation in between. Although rapid onset of action (15–45 minutes is a noteworthy merit of intramuscular drugs, such an invasive strategy is far too often bound to patients’ anxiety, resistance, and traumatic experiences. The need for novel drug formulations (ideally, both integrating the benefits of injectable and orally administered tranquillizing medications, and free from their disadvantages can be, therefore, clearly grasped. Development of inhaled loxapine exemplifies the attempts to overcome the above-delineated obstacles. As suggested by the available research base, inhaled loxapine seems to be an effective anti-agitation drug in treatment of patients with schizophrenia and BD (with the onset of action similar to the one observed in intramuscular antipsychotics. However, this formulation of loxapine is distinguished by its non-invasive route of administration, as accompanied by markedly low risk of side effects or adverse events.

  16. Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs. (United States)

    Hesterberg, T W; Miiller, W C; Thevenaz, P; Anderson, R


    Inhalation studies were conducted to determine the chronic biological effects in rodents of respirable fractions of different man-made vitreous fibres (MMVFs), including refractory ceramic fibre (RCF), fibrous glass, rock (stone) wool and slag wool. Animals were exposed nose-only, 6 h per day, 5 days per week, for 18 months (hamsters) or 24 months (rats). Exposure to 10 mg m-3 of crocidolite or chrysotile asbestos induced pulmonary fibrosis, lung tumours and mesothelioma in rats, thus validating the inhalation model with known human carcinogenic fibres. Exposure of rats to 30 mg m-3 of refractory ceramic fibres (RCF) also resulted in pulmonary fibrosis as well as significant increases in lung tumours and mesothelioma. In hamsters, 30 mg m-3 of RCF induced a 41% incidence of mesotheliomas. Exposure of rats to 30 mg m-3 of fibre glasses (MMVF 10 or 11) or of slag wool (MMVF 22) was associated with an inflammatory response, but no mesotheliomas or significant increase in the lung tumours were observed. Rock wool (stone wool: MMVF 21) at the same exposure level resulted in minimal lung fibrosis, but no mesotheliomas or significant increase in the lung tumours were observed. Fibre numbers (WHO fibres) and dimensions in the aerosols and lungs of exposed animals were comparable in this series of inhalation studies. Differences in lung fibre burdens and lung clearance rates could not explain the differences observed in the toxicologic effects of the MMVFs. These findings indicate that dose, dimension and durability may not be the only determinants of fibre toxicity. Chemical composition and the surface physico-chemical properties of the fibres may also play an important role.

  17. Development of cyclosporine A-loaded dry-emulsion formulation using highly purified glycerol monooleate for safe inhalation therapy. (United States)

    Sato, Hideyuki; Ogawa, Kumiko; Kojo, Yoshiki; Kawabata, Yohei; Mizumoto, Takahiro; Yamada, Shizuo; Onoue, Satomi


    The main objective of this study was to improve the safety and oxidative stability of glycerol monooleate (GMO)-based dry-emulsion (DE) formulation containing cyclosporine A (CsA) for inhalation therapy. GMO or highly purified GMO (hpGMO) was used as surfactant for the DE formulations (GMO/DE or hpGMO/DE), the toxicological and physicochemical properties of which were characterized with a focus on oxidative stability, in vitro/in vivo toxicity, and dissolution property. Incubation of GMO at oxidation accelerating conditions for 10 days at 60°C resulted in the formation of lipid peroxides as evidenced by increased malondialdehyde (111 μmol/mg); however, hpGMO samples exhibited increase of only 20.7 μmol/mg in malondialdehyde level. No significant acute cytotoxicity was observed in rat alveolar L2 cells exposed to hpGMO (0.28mM), and intratracheal administration of hpGMO powder in rats did not cause an increase of the plasma LDH level. The hpGMO/DE exhibited marked improvement in dissolution behavior of CsA, and stable fine micelles with a mean diameter of 320 nm were formed when suspended in water. A respirable powder formulation of hpGMO/DE (hpGMO/DE-RP) was newly prepared, and its in vitro inhalation property and in vivo efficacy were also evaluated. The hpGMO/DE-RP exhibited high dispersibility in laser diffraction analysis and significantly improved potency to attenuate recruitment of inflammatory cells into airway and thickening of airway wall in an animal model. Thus, the strategic use of hpGMO would improve oxidative stability and local toxicity compared with a GMO-based DE formulation, and its application to RP formulation could be a promising approach for effective inhalation therapy.

  18. No effect of pure oxygen inhalation on headache induced by glyceryl trinitrate

    DEFF Research Database (Denmark)

    Daugaard, D.; Tfelt-Hansen, P.; Thomsen, L.L.


    Inhalation of hyperbaric oxygen has been used as an experimental treatment for migraine and pure oxygen is an established treatment for cluster headache. Intravenous glyceryl trinitrate (GTN) is an established headache model. In the present study the possibility of decreasing the headache...... by inhalation of pure oxygen was explored in a double-blind crossover design in 18 healthy subjects. Inhalation of air served as placebo. The subjects received intravenous GTN (0.25 A mu g/kg/min) for 20 min. Headache was scored for 85 min. Sixteen of 18 (89%) subjects experienced GTN-induced headache after O-2......-inhalation and 17/18 (94%) experienced GTN-induced headache after air. The mean peak headache scores were 1.9 and 2.4, respectively, on a numerical scale of 0-10. Oxygen inhalation did not have effect on GTN-induced headache, most likely because the theoretical decrease in NO levels, due to faster metabolism...

  19. Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis. (United States)

    Vazquez-Espinosa, E; Marcos, C; Alonso, T; Giron, R M; Gomez-Punter, R M; Garcia-Castillo, E; Zamora, E; Cisneros, C; Garcia, J; Valenzuela, C; Ancochea, J


    Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.

  20. Importance of light smoking and inhalation habits on risk of myocardial infarction and all cause mortality. A 22 year follow up of 12 149 men and women in The Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Prescott, E; Scharling, H; Osler, M


    . After adjusting for major cardiovascular risk factors there was a dose-response relation between smoking with and without inhaling and both MI and all cause mortality. Among inhaling smokers significantly increased risks were found in women at a consumption of only 3-5 grams of tobacco per day...... with higher RR found in women than in men. The study emphasises the importance of recognising that even very limited tobacco consumption has detrimental health effects........30)). The RR associated with smoking were significantly higher in women than in men for both MI and all cause mortality. CONCLUSIONS: Smoking as little as 3-5 grams of tobacco per day or not inhaling the smoke was shown to carry a significantly increased risk of developing MI and of all cause mortality...