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Sample records for dose inhaler mdi

  1. Evaluation of an abbreviated impactor for fine particle fraction (FPF) determination of metered dose inhalers (MDI).

    PubMed

    Guo, Changning; Ngo, Diem; Ahadi, Shafiq; Doub, William H

    2013-09-01

    Abbreviated impactors have been developed recently to allow more rapid evaluation of inhalation products as alternates to the eight-stage Andersen Cascade Impactor (ACI) which has been widely used in the pharmaceutical industry for assessing aerodynamic particle size distribution. In this paper, a two-stage abbreviated impactor, Westech Fine Particle Dose Impactor (WFPD), was used to characterize the aerodynamic particle size of metered dose inhaler (MDI) products, and the results were compared with those obtained using the standard eight-stage ACI. Seven commercial MDI products, with different propellants (chlorofluorocarbon/hydrofluoroalkane) and formulation types (suspension/solution, dry/normal/wet), were tested in this study by both WFPD and ACI. Substantially equivalent measures of fine particle fraction were obtained for most of the tested MDI products, but larger coarse particle fraction and extra-fine particle fraction values were measured from WFPD relative to those measured using the ACI. Use of the WFPD also produced more wall loss than the ACI. Therefore, it is recommended that the system suitability be evaluated on a product-by-product basis to establish substantial equivalency before implementing an abbreviated impactor measurement methodology for routine use in inhaler product characterization. PMID:23780781

  2. Rapid interrogation of the physical and chemical characteristics of salbutamol sulphate aerosol from a pressurised metered-dose inhaler (pMDI).

    PubMed

    Tong, H-J; Fitzgerald, C; Gallimore, P J; Kalberer, M; Kuimova, M K; Seville, P C; Ward, A D; Pope, F D

    2014-12-21

    Individual micron-sized solid particles from a Salamol® pharmaceutical inhaler are stably captured in air using an optical trap for the first time. Raman spectroscopy of the levitated particles allows online interrogation of composition and deliquescent phase change within a high humidity environment that mimics the particle's travel from inhaler to lung. PMID:25329335

  3. Dermal and inhalation exposure to methylene bisphenyl isocyanate (MDI) in iron foundry workers.

    PubMed

    Liljelind, I; Norberg, C; Egelrud, L; Westberg, H; Eriksson, K; Nylander-French, L A

    2010-01-01

    Diisocyanates are a group of chemically reactive agents, which are used in the production of coatings, adhesives, polyurethane foams, and parts for the automotive industry and as curing agents for cores in the foundry industry. Dermal and inhalation exposure to methylene bisphenyl isocyanate (MDI) is associated with respiratory sensitization and occupational asthma. However, limited research has been performed on the quantitative evaluation of dermal and inhalation exposure to MDI in occupationally exposed workers. The objective of this research was to quantify dermal and inhalation exposure levels in iron foundry workers. Workers involved in mechanized moulding and mechanized production of cores were monitored: 12 core makers, 2 core-sand preparers, and 5 core installers. Personal breathing-zone levels of MDI were measured using impregnated filter sampling. Dermal exposure to MDI was measured using a tape-strip technique. Three or five consecutive tape-strip samples were collected from five exposed skin areas (right and left forefingers, left and right wrists, and forehead). The average personal air concentration was 0.55 microg m(-3), 50-fold lower than the Swedish occupational exposure limit of 30 microg m(-3). The core makers had an average exposure of 0.77 microg m(-3), which was not significantly different from core installers' and core-sand preparers' average exposure of 0.16 microg m(-3) (P = 0.059). Three core makers had a 10-fold higher inhalation exposure than the other core makers. The core makers' mean dermal exposure at different skin sites varied from 0.13 to 0.34 microg while the two other groups' exposure ranged from 0.006 to 0.062 microg. No significant difference was observed in the MDI levels between the skin sites in a pairwise comparison, except for left forefinger compared to left and right wrist (P < 0.05). In addition, quantifiable but decreasing levels of MDI were observed in the consecutive tape strip per site indicating MDI penetration

  4. A multiple dose powder inhaler (Turbuhaler) compared with a conventional aerosol. An acceptance study in asthmatics.

    PubMed

    Osterman, K; Norborg, A M; Stähl, E

    1989-05-01

    Nineteen patients with asthma completed an open, randomized, crossover study in which 0.5 mg terbutaline sulphate was administered either via Turbuhaler or via the metered dose inhaler (MDI) for 2-week periods. The clinical effect of the two treatment forms was comparable; both provided adequate bronchodilator therapy. Patients also considered Turbuhaler and MDI equally effective, with a small preference for the MDI. Turbuhaler seems to be a valuable alternative to bronchodilator MDI therapy. PMID:2735519

  5. Inhaled Asthma Medications

    MedlinePlus

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    1989-09-01

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

  8. Reservoir design and dose availability with long-term metered dose inhaler corticosteroid use.

    PubMed

    Rau, J L; Zhu, Y

    1998-01-01

    The effect of reservoir design and long-term use with inhaled metered dose inhaler (MDI) corticosteroids on aerosol dose availability was examined. Beclomethasone dipropionate (Vanceril) was delivered by MDI with three brands of available reservoir devices: the AeroChamber, the OptiHaler, and the Aerosol Cloud Enhancer (ACE). An in vitro lung model simulated inspiration. Long-term use was simulated by exhausting five MDI canisters of beclomethasone through each sample of reservoir tested. Each canister exhausted through a reservoir represented approximately 1 month of use with one drug. Total inhaled dose was collected at the reservoir mouthpiece and measured using a spectrophotometric assay. Dose delivery was measured before simulated use and after each MDI canister was exhausted through the reservoir. Three samples of each brand were tested with cleaning and three samples were tested without cleaning. With cleaning, the AeroChamber, OptiHaler, and ACE delivered significantly different average doses of 16.6, 10.3, and 8.7 micrograms per MDI actuation, respectively, (P = 0.0017) over time of use. Changes in dose delivery over time of use were not significant (P = 0.2011). Without cleaning, the same three brands averaged 21.1, 9.7, and 7.8 micrograms per MDI actuation, respectively, (P = 0.0019), and changes in dose delivery over time were not significant (P = 0.3265). Reservoir design can affect the delivery of an inhaled corticosteroid, although the delivery over 4 to 5 months remained stable. PMID:10177218

  9. Plume temperature emitted from metered dose inhalers.

    PubMed

    Brambilla, G; Church, T; Lewis, D; Meakin, B

    2011-02-28

    The temperature of the drug cloud emitted from a pressurised metered dose inhaler (pMDI) may result in patient discomfort and inconsistent or non-existent dose delivery to the lungs. The effects of variations in formulation (drug, propellant, co-solvent content) and device hardware (metering volume, actuator orifice diameter, add-on devices) upon the temperature of pMDI plumes, expressed as replicate mean minimum values (MMPT), collected into a pharmacopoeial dose unit sampling apparatus (DUSA), have been investigated. Ten commercially available and two development products, including chlorofluorocarbon (CFC) suspensions and hydrofluoroalkane (HFA) solutions or suspensions, were examined together with a number of drug products in late stage development and a variety of HFA 134a placebo pMDIs. Plume temperatures were observed to be lowest in the proximity of the product's actuator mouthpiece where rapid flashing and evaporation of the formulation's propellant and volatile excipients cause cooling. The ability to control plume temperature by judicious choice of formulation co-solvent content, metering volume and the actuator orifice diameter is identified. An ethanol based HFA 134a formulation delivered through a fine orifice is inherently warmer than one with 100% HFA 134a vehicle delivered through a coarse actuator orifice. Of the 10 commercial products evaluated, MMPTs ranged from -54 to +4°C and followed the formulation class rank order, HFA suspensionsMDI plume temperature to that of the ambient surroundings by use of an add-on or integrated spacer device. PMID:21129465

  10. Factors affecting total and "respirable" dose delivered by a salbutamol metered dose inhaler.

    PubMed Central

    Everard, M. L.; Devadason, S. G.; Summers, Q. A.; Le Souëf, P. N.

    1995-01-01

    BACKGROUND--Many factors contribute to the high variability of doses delivered to the lungs of patients using metered dose inhalers (MDIs). Relatively little attention has been paid to the contribution to this variability of the way in which the MDI is handled before the inhalation manoeuvre. Instruction leaflets often recommend procedures at odds with those used for in vitro testing of the device. The standard protocol for in vitro assessment of salbutamol MDIs involves shaking the MDI vigorously for 30 seconds and wasting the first two actuations. Subsequent actuations are introduced into the testing device at five second intervals. Patient instructions do not include a recommendation to waste the first two actuations and recommend a delay of one minute between actuations. A series of experiments was performed to determine whether such differences might be important. METHODS--The total and "respirable" doses delivered by a salbutamol MDI (Ventolin, Allen & Hanburys) under various conditions were assessed with a multistage liquid impinger. The quantity of drug deposited on each stage was measured by an ultraviolet spectrophotometric method. The effect on the delivered dose of not shaking the canister, not wasting the first two doses, waiting 30 seconds between actuations, and using multiple rapid actuations was assessed by comparing the results with those obtained using the standard in vitro testing protocol. RESULTS--Compared with a standard protocol, it was found that not shaking the MDI before use reduced the total and "respirable" dose by 25.5% and 35.7%, respectively. The dose delivered when actuating the MDI at 30 second intervals was no different from that when intervals was no different from that when intervals of five seconds were used. Two actuations separated by one second had no effect on the total dose but reduced the "respirable" dose by 15.8%, while four rapid actuations reduced the total and "respirable" doses by 8.2% and 18.2%, respectively

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

    PubMed

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

    1996-10-01

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

  12. Comparison of effectiveness and time-efficiency between multimedia and conventional counselling on metered-dose inhaler technique education

    PubMed Central

    King, Teck Long; Kho, Evelyn Kui Yee; Tiong, Yiek Hung; Julaihi, Siti Norhajariah Binti

    2015-01-01

    INTRODUCTION This study aimed to evaluate whether multimedia counselling (MC) using a touchscreen computer is as effective and time-efficient as conventional counselling (CC) in promoting correct metered-dose inhaler (MDI) technique, with or without the valved holding chamber (VHC). METHODS Participants in the MDI-only and MDI-with-VHC groups were randomly assigned to the MC group or CC group. No blinding was imposed. Inhalation technique was assessed using checklists before and after counselling. Time spent on counselling was determined for all participants, while time taken to perfect the technique was determined only for participants who achieved perfect technique within one hour. RESULTS The CC group had more elderly participants than the MC group, but the difference was not significant. MDI-only and MDI-with-VHC users showed significant improvement in their inhaler technique after multimedia (44.5 ± 28.0% and 44.1 ± 14.4%, respectively) and conventional counselling (36.8 ± 20.5% and 37.0 ± 14.6%, respectively). No significant difference in MDI technique enhancement was found between the two groups. Although no significant difference was found between the MC and CC groups with regard to the time spent on counselling and the time taken to perfect the technique, the average time spent on counselling was longer for MDI-only users. MDI-only users had 13.5 times the odds of failing to achieve perfect technique compared to MDI-with-VHC users (95% confidence interval 1.50–121.32, p = 0.020). CONCLUSION MC and CC significantly improved MDI technique. Both methods showed comparable short-term effectiveness and time-efficiency in MDI technique education. VHC was beneficial, especially for MDI-users with hand-lung coordination problems. PMID:25715856

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

    PubMed

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

    2014-04-01

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

  14. Budesonide/formoterol pressurized metered-dose inhaler: in chronic obstructive pulmonary disease.

    PubMed

    Lyseng-Williamson, Katherine A

    2009-07-30

    The corticosteroid budesonide and the rapid-onset, long-acting beta(2)-adrenoceptor agonist formoterol have been combined into a single pressurized metered-dose inhaler (pMDI) for use in patients with chronic obstructive pulmonary disease (COPD). Well designed 6- and 12-month clinical trials, twice-daily budesonide/formoterol pMDI 320 microg/9 microg effectively improved lung function in patients with moderate to very severe COPD. The co-primary endpoints of adjusted mean morning predose forced expiratory volume in 1 second (FEV(1)) and 1-hour post-dose FEV(1) improved from baseline to a significantly greater extent with twice-daily budesonide/formoterol pMDI 320 microg/9 microg than with twice-daily placebo, budesonide pMDI 320 microg and formoterol dry powder inhaler 9 microg. Budesonide/formoterol pMDI was also associated with improvements from baseline in other measures of lung function, COPD control (including the time to first COPD exacerbation in the 12-month trial), symptoms and health status. These improvements were significantly greater than those observed with placebo and, for some endpoints, monotherapy with the individual components. Budesonide/formoterol pMDI was well tolerated in clinical trials in patients with COPD. Its overall adverse event profile is consistent with the known tolerability profiles of formoterol and budesonide, and is generally similar to that with placebo. PMID:19634924

  15. Advances in metered dose inhaler technology: hardware development.

    PubMed

    Stein, Stephen W; Sheth, Poonam; Hodson, P David; Myrdal, Paul B

    2014-04-01

    Pressurized metered dose inhalers (MDIs) were first introduced in the 1950s and they are currently widely prescribed as portable systems to treat pulmonary conditions. MDIs consist of a formulation containing dissolved or suspended drug and hardware needed to contain the formulation and enable efficient and consistent dose delivery to the patient. The device hardware includes a canister that is appropriately sized to contain sufficient formulation for the required number of doses, a metering valve capable of delivering a consistent amount of drug with each dose delivered, an actuator mouthpiece that atomizes the formulation and serves as a conduit to deliver the aerosol to the patient, and often an indicating mechanism that provides information to the patient on the number of doses remaining. This review focuses on the current state-of-the-art of MDI hardware and includes discussion of enhancements made to the device's core subsystems. In addition, technologies that aid the correct use of MDIs will be discussed. These include spacers, valved holding chambers, and breath-actuated devices. Many of the improvements discussed in this article increase the ability of MDI systems to meet regulatory specifications. Innovations that enhance the functionality of MDIs continue to be balanced by the fact that a key advantage of MDI systems is their low cost per dose. The expansion of the health care market in developing countries and the increased focus on health care costs in many developed countries will ensure that MDIs remain a cost-effective crucial delivery system for treating pulmonary conditions for many years to come. PMID:24357110

  16. Bronchodilator effect of single-dose formoterol administered by pressurized metered-dose inhaler in children with asthma aged 6 to <12 years receiving budesonide.

    PubMed

    Berger, William E; Gillen, Michael; Eckerwall, Göran; Uryniak, Tom; Trudo, Frank J; Lampl, Kathy L

    2014-01-01

    Dose-response of formoterol via pressurized metered-dose inhaler (pMDI) has not been determined in asthmatic pediatric patients aged 6 to <12 years. This study was designed to assess the bronchodilating dose-response of three formoterol pMDI doses in children with stable asthma aged 6 to <12 years receiving twice-daily (b.i.d.) budesonide 160 micrograms. A U.S., multicenter, five-way crossover study compared single doses of formoterol, a long-acting beta-agonist, via pMDI (2.25, 4.5, and 9 micrograms) or dry powder inhaler (12 micrograms; active comparator) and placebo, with a 3- to 14-day washout period between doses. Budesonide pMDI 160 micrograms, an inhaled corticosteroid, was given b.i.d. throughout the study. Fifty-four pediatric patients (mean age, 9.2 years; mean asthma history, 6.1 years) were randomized. All formoterol doses showed significantly higher average 12-hour forced expiratory volume in 1 second (FEV1; area under the curve) versus placebo (primary efficacy). Formoterol pMDI 4.5 and 9 micrograms showed significantly greater average 12-hour FEV1 than formoterol 2.25 micrograms (p = 0.0007 and p = 0.0001, respectively). Formoterol also resulted in significant improvement in maximum FEV1 during the 12-hour treatment period (secondary efficacy) with formoterol 4.5-, 9-, and 12-microgram doses versus placebo and the formoterol 2.25-microgram dose. Bronchodilation was not maintained during the 12-hour dosing interval with formoterol 2.25 micrograms. No serious adverse events were reported. Formoterol pMDI showed generally dose-proportional pharmacokinetics to 9 micrograms, as determined by urinary excretion. Single doses of formoterol pMDI showed a dose-response, with formoterol 9 micrograms exhibiting a maximum response, in pediatric patients aged 6 to <12 years with persistent stable asthma maintained on b.i.d. budesonide pMDI 160 micrograms. Clinical trial NCT01136655, www.clinicaltrials.gov. PMID:24717790

  17. A Rationale for Going Back to the Future: Use of Disposable Spacers for Pressurised Metered Dose Inhalers

    PubMed Central

    Sanders, Mark; Bruin, Ronald

    2015-01-01

    The introduction of pressurised metered dose inhalers (MDIs) in the mid-1950s completely transformed respiratory treatment. Despite decades of availability and healthcare support and development of teaching aids and devices to promote better use, poor pMDI user technique remains a persistent issue. The main pMDI user aid is the spacer/valved holding chamber (VHC) device. Spacer/chamber features (size, shape, configuration, construction material, and hygiene considerations) can vie with clinical effectiveness (to deliver the same dose as a correctly used pMDI), user convenience, cost, and accessibility. Unsurprisingly, improvised, low-cost alternatives (plastic drink bottles, paper cups, and paper towel rolls) have been pressed into seemingly effective service. A UK law change permitting schools to hold emergency inhalers and spacers has prompted a development project to design a low-cost, user-friendly, disposable, and recyclable spacer. This paper spacer requires neither preuse priming nor washing, and has demonstrated reproducible lung delivery of salbutamol sulphate pMDI, comparable to an industry-standard VHC, an alternative paperboard VHC, and pMDI alone. This new device appears to perform better than these other VHC devices at the low flow rates thought achievable by paediatric patients. The data suggest that this disposable spacer may have a place in the single-use emergency setting. PMID:26491563

  18. A Rationale for Going Back to the Future: Use of Disposable Spacers for Pressurised Metered Dose Inhalers.

    PubMed

    Sanders, Mark; Bruin, Ronald

    2015-01-01

    The introduction of pressurised metered dose inhalers (MDIs) in the mid-1950s completely transformed respiratory treatment. Despite decades of availability and healthcare support and development of teaching aids and devices to promote better use, poor pMDI user technique remains a persistent issue. The main pMDI user aid is the spacer/valved holding chamber (VHC) device. Spacer/chamber features (size, shape, configuration, construction material, and hygiene considerations) can vie with clinical effectiveness (to deliver the same dose as a correctly used pMDI), user convenience, cost, and accessibility. Unsurprisingly, improvised, low-cost alternatives (plastic drink bottles, paper cups, and paper towel rolls) have been pressed into seemingly effective service. A UK law change permitting schools to hold emergency inhalers and spacers has prompted a development project to design a low-cost, user-friendly, disposable, and recyclable spacer. This paper spacer requires neither preuse priming nor washing, and has demonstrated reproducible lung delivery of salbutamol sulphate pMDI, comparable to an industry-standard VHC, an alternative paperboard VHC, and pMDI alone. This new device appears to perform better than these other VHC devices at the low flow rates thought achievable by paediatric patients. The data suggest that this disposable spacer may have a place in the single-use emergency setting. PMID:26491563

  19. Metering performance of several metered-dose inhalers with different spacers/holding chambers.

    PubMed

    Berlinski, A; Waldrep, J C

    2001-01-01

    Metered-dose inhalers (MDI) are routinely used to administer inhaled antiasthma drugs. Actuation-inhalation coordination problems are overcome and systemic side effects are reduced by using spacers/holding chambers (SP/HCHs). Many of these devices do not allow the use of the manufacturer's actuator. The objectives of this study were (a) to investigate the effect of the interaction of eight MDI products with four different SP/HCHs on their metering performance (MP); and (b) to test the hypothesis whether the MP obtained with a SP/HCH and a given drug (MDI) can be extrapolated to other MDIs, even for members of its particular drug class. The procedure outlined in The United States Pharmacopeia-The National Formulary was used (determination of canister weight changes after actuation). The SP/HCH tested were Aerochamber, Inspirease, and ACE. The MDIs tested were salmeterol xinafoate; albuterol with chlorofluorocarbons and 1,1,1,2-tetrafluoroethane as propellants; cromolyn sodium; nedocromil sodium; flunisolide; beclomethasone dipropionate; and fluticasone propionate. Only flunisolide-Inspirease presented an unacceptable MP. Although within the acceptable limits, the MP varied significantly between the following MDI-SP/HCH combinations: Optihaler-fluticasone propionate and Optihaler-cromolyn sodium < to Aerochamber-fluticasone propionate and Aerochamber-cromolyn sodium (p = 0.0015 and p = 0.0007, respectively); and Inspirease-flunisolide and Optihaler-flunisolide < Aerochamber flunisolide (p = 0.003 and p = 0.005, respectively). MP did not significantly vary when albuterol with chlorofluorocarbons or 1,1,1,2-tetrafluoroethane as propellants, salmeterol xinafoate, beclomethasone dipropionate, and nedocromil sodium were attached to any of the SP/HCHs studied. Our results emphasize the capital importance of choosing the right combination of MDI and SP/HCH for aerosol delivery. The MP obtained with a drug and a SP/HCH cannot be expected to be similar for other MDIs, even

  20. Efficiency of Ipratropium Bromide and Albuterol Deposition in the Lung Delivered via a Soft Mist Inhaler or Chlorofluorocarbon Metered-Dose Inhaler.

    PubMed

    MacGregor, T R; ZuWallack, R; Rubano, V; Castles, M A; Dewberry, H; Ghafouri, M; Wood, C C

    2016-04-01

    The propellant-free Combivent Respimat Soft Mist Inhaler (CVT-R) was developed to replace the chlorofluorocarbon-propelled Combivent metered-dose inhaler (CVT-MDI). This steady-state pharmacokinetic (PK) substudy evaluated drug lung-delivery efficiency, using data from two phase III safety and efficacy trials. PK parameters were obtained from well-controlled population PK analyses. Area under the plasma concentration-time curve (AUC), maximum observed plasma concentration (C(max)), and minimum observed plasma concentration (C(min)) showed systemic exposure to ipratropium bromide and albuterol delivered via the CVT-R was proportional to ex-mouthpiece delivered dose. Although the labeled dose of ipratropium bromide in the CVT-R was half that in the CVT-MDI, the systemic exposure was comparable. No PK interaction for the ipratropium bromide and albuterol Respimat drug components was demonstrated. Ipratropium bromide alone resulted in similar exposure to the combination of ipratropium bromide and albuterol. These results show that CVT-R delivers drug more efficiently to the lung than CVT-MDI. PMID:26945929

  1. Predicting physical stability in pressurized metered dose inhalers via dwell and instantaneous force colloidal probe microscopy.

    PubMed

    D'Sa, Dexter; Chan, Hak-Kim; Chrzanowski, Wojciech

    2014-09-01

    Colloidal probe microscopy (CPM) is a quantitative predictive tool, which can offer insight into particle behavior in suspension pressurized metered dose inhalers (pMDIs). Although CPM instantaneous force measurements, which involve immediate retraction of the probe upon sample contact, can provide information on inter-particle attractive forces, they lack the ability to appropriately imitate all critical particle pMDI interactions (e.g., particle re-dispersion after prolonged pMDI storage). In this paper, two novel dwell force techniques - indentation and deflection dwell - were employed to mimic long-term particle interactions present in pMDIs, using particles of various internal structures and a model liquid propellant (2H,3H perfluoropentane) as a model system. Dwell measurements involve particle contact for an extended period of time. In deflection dwell mode the probe is held at a specific position, while in indentation dwell mode the probe is forced into the sample with a constant force for the entirety of the contact time. To evaluate the applicability of CPM to predict actual pMDI physical stability, inter-particle force measurements were compared with qualitative and quantitative bulk pMDI measurement techniques (visual quality and light scattering). Measured instantaneous attractive (snap-in) and adhesive (max-pull) forces decreased as a function of increasing surface area, while adhesive forces measured by indentation dwell decreased as a function of dwell contact time for particles containing voids. Instantaneous force measurements provided information on the likelihood of floccule formation, which was predictive of partitioning rates, while indentation dwell force measurements were predictive of formulation re-dispersibility after prolonged storage. Dwell force measurements provide additional information on particle behavior within a pMDI not obtainable via instantaneous measurements. PMID:25058596

  2. Metered dose inhaler add-on devices: is the inhaled mass of drug dependent on the size of the infant?

    PubMed

    Turpeinen, M; Nikander, K; Malmberg, L P; Pelkonen, A

    1999-01-01

    Limited cooperation and low tidal volumes in infants make aerosol therapy difficult. We measured the amount of drug delivered from two baby spacer devices especially developed for use in infants. Designed as a randomized crossover study, aerolized budesonide from a pressurized metered dose inhaler (pMDI) was collected in the inspiratory filter interposed between the face mask and the spacer in 13 infants aged from 2 to 19 months old. The study was performed in connection with pulmonary function testing with a plethysmograph, and the children were sedated with cloral hydrate. Two small-volume baby spacer devices were used: a Babyhaler spacer (GlaxoWellcome, Hertfordshire, UK) made of polycarbonate with a volume of 350 mL and a built-in dead space of 40 mL and a NebuChamber spacer (AstraZeneca, Lund, Sweden) made of stainless steel with a volume of 250 mL and no dead space. Budesonide delivery from the NebuChamber was significantly higher than from the Babyhaler: 38.2% (range, 28.3%-47.5%) of the nominal dose versus 12% (range, 3.3%-21.25%) of the nominal dose of 400 micrograms of budesonide (P = 0.002). The inhaled mass of budesonide from the Babyhaler correlated significantly with skin surface area (r = 0.68, P = 0.018), weight (r = 0.66, P = 0.019), height (r = 0.69; P = 0.017), tidal volume (r = 0.82; P = 0.004), and minute volume (r = 0.67; P = 0.019). No correlations were found between these variables and the inhaled mass of budesonide from the NebuChamber. The results indicate that the design of the NebuChamber spacer affords stable drug delivery in infants and that a large variability in the inhaled mass of drug may be found when infants are inhaling from different baby spacers. PMID:10623333

  3. Comparison of the clinical effects of combined salmeterol/fluticasone delivered by dry powder or pressurized metered dose inhaler.

    PubMed

    Hojo, Masayuki; Shirai, Toshihiro; Hirashima, Junko; Iikura, Motoyasu; Sugiyama, Haruhito

    2016-04-01

    The salmeterol/fluticasone combination (SFC) inhaler is currently the most widely used maintenance drug for asthmatics worldwide. Although the effectiveness of SFC as either a dry powder inhaler (DPI) or a pressurized metered dose inhaler (pMDI) is well documented, there is limited data comparing the clinical efficacies of the two devices. To address this issue, we carried out a randomized crossover trial in which asthmatic patients (n = 47; mean age, 62.5 ± 16.5 years old) received a 12-week treatment of SFC DPI (50/250 μg twice daily) or SFC pMDI (four puffs of 25/125 μg daily). After a 4-week washout period, patients received another crossover treatment for 12 weeks. Respiratory resistance and reactance were measured by forced oscillation technique (MostGraph-01), spirometry, fractional exhaled nitric oxide (FeNO), and an asthma control test (ACT) every 4 weeks. The mean forced expiratory volume1.0 at the baseline was 2.16 ± 0.86 (L). Respiratory system resistance at 5 Hz (R5), the difference between R5 and R at 20 Hz (R5 - R20), and FeNO improved in both treatment groups, while reactance at 5 Hz (X5) and ACT score improved only in the pMDI group. In patients >70 years old (n = 21), R5, R5 - R20, ΔX5, and FeNO improved only in the pMDI group. These results suggest that SFC by pMDI produces a stronger anti-inflammatory and bronchodilatory effect even in patients whose asthma is well controlled by SFC delivered by DPI. PMID:26898348

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

    PubMed Central

    2011-01-01

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

  5. Deposition and clinical efficacy of terbutaline sulphate from Turbuhaler, a new multi-dose powder inhaler.

    PubMed

    Newman, S P; Morén, F; Trofast, E; Talaee, N; Clarke, S W

    1989-03-01

    A radioaerosol technique has been developed in order to assess deposition patterns from a new metered dose powder inhaler (Turbuhaler, Astra Pharmaceuticals). The radionuclide Tc99m dissolved in chloroform was added to a spheronised formulation of micronised terbutaline sulphate and the chloroform was allowed to evaporate. Turbuhaler subsequently delivered 0.5 mg of treated drug per metered dose. In vitro tests with a multistage liquid impinger showed that the fractionation of the drug dose between different particle size bands was similar to the fractionation of radioactivity. In a group of ten asthmatic patients, a mean 14.2% (SEM 2.1) of the drug dose was deposited in the lungs, with 71.6% (3.0) of the dose in the oropharynx. Of the remainder, 13.7% (2.1) was deposited on the mouthpiece, and 0.5% (0.2) recovered from exhaled air. The radiolabel was present in both central and peripheral zones of the lungs. All patients bronchodilated; forced expiratory volume in one second (FEV1) increased from 1.40 (0.24) l to 1.77 (0.24) l (p less than 0.01) 20 min after inhalation. These results suggest that both the distribution of drug and the clinical effect of terbutaline sulphate delivered from Turbuhaler are similar to those from a pressurised metered dose inhaler (MDI). PMID:2731602

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

    PubMed

    D'Sa, Dexter; Chan, Hak-Kim

    2015-01-01

    Advances in particle engineering techniques, such as spray drying, freeze drying and supercritical fluid precipitation, have greatly enhanced the ability to control the structure, morphology, and solid state phase of inhalable sized particles (1 - 5 µm) for formulation in pressurized metered dose inhalers (pMDI). To optimize the properties of these engineered particles for formulation in hydrofluoroalkane propellants (HFA 134a / 227) it is necessary to measure both bulk and individual particle properties before, after, and during formulation. This review examines established and recently developed methods for evaluating a variety of particle properties including but not limited to size, surface and internal morphology, chemical composition, and solid state phase. Novel methods for evaluating particle physical and chemical stability directly in propellant or similar environments are also discussed. PMID:26290200

  7. Cosuspensions of microcrystals and engineered microparticles for uniform and efficient delivery of respiratory therapeutics from pressurized metered dose inhalers.

    PubMed

    Vehring, Reinhard; Lechuga-Ballesteros, David; Joshi, Vidya; Noga, Brian; Dwivedi, Sarvajna K

    2012-10-23

    Engineered porous phospholipid microparticles with aerodynamic diameters in the respirable range of 1-2 μm were cosuspended in 1,1,1,2-tetrafluoroethane, a propellant, with microcrystals of glycopyrrolate, formoterol fumarate dihydrate, or Mometasone furoate-three drugs with different solubilities in the propellant, and different physical, chemical, and pharmacological attributes. The drug microcrystals were added individually, in pairs, or all three together to prepare different cosuspensions, contained in a pressurized metered dose inhaler (pMDI). The drug microcrystals irreversibly associated with the porous particles, and the resultant cosuspensions possessed greatly improved suspension stability compared with suspensions of drug microcrystals alone. In general, all cosuspensions showed efficient dose delivery of the drugs, with fine particle fractions of more than 60% for a wide range of doses, including those as low as 300 ng per inhaler actuation. In the cosuspension pMDIs, comparable fine particle fractions were delivered for all tested drugs, whether or not they were emitted from an inhaler containing one, two, or three drugs. We demonstrate that the cosuspension approach solves at least three long-standing problems in the clinical development of pMDI-based products: (1) dose and drug dependent delivery efficiency, (2) inability to formulate dose strengths below 1 μg to fully explore drug efficacy and safety, and (3) combination suspensions delivering a different fine particle fraction than individual drug suspensions. PMID:22985189

  8. Metered dose inhaler salbutamol treatment of asthma in the ED: comparison of two doses with plasma levels.

    PubMed

    Rodrigo, G; Rodrigo, C

    1996-03-01

    Two cumulative doses of salbutamol delivered by metered dose inhaler (MDI) with a pear-shaped spacer were compared (400 micrograms vs 600 micrograms at 10-minute intervals). Twenty-two patients (mean age 35.1 +/- 11.1 years) with acute exacerbation of asthma were randomly selected, in a double-blind fashion, to receive salbutamol delivered with MDI into a spacer device in 4 puffs at 10- minute intervals (100 micrograms or 150 micrograms per actuation) during 3 hours (1200 micrograms or 1800 micrograms each 30 minutes). Mean peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1) improved significantly over baseline values for both groups (P < .001). Nevertheless, there were no significant differences between both groups for PEFR and FEV1 at any time point studied. A significant net reduction of heart rate was observed in the 400 microgram group (P < .01). On the other hand, a significant increase in heart rate was observed in the 600 microgram group (P < .001). The QTc interval did not show a significant prolongation, and the two groups presented moderate decreases of serum potassium levels. There was a significant dose-related increase (P = .027) in Sao2. Additionally, the 600 microgram group generated a serum glucose level increase from 0.85 +/- 0.12 mg/100 mL to 1.04 +/- 0.25 mg/100 mL (P = .02), with a higher incidence in 4 symptoms (tremor, headache, palpitations, and anxiety). These data support the notion that the treatment of acute asthma patients in the emergency department setting with salbutamol, 2.4 mg/h, delivered by MDI and spacer (4 puffs at 10-minute intervals) produces satisfactory bronchodilation, low serum concentration, and minimal extrapulmonary effects. However, an increase of 50% of the dose (600 micrograms at 10-minute intervals) produced a nonsignificant, slightly better therapeutic response but with greater side effects, probably related to higher salbutamol levels. PMID:8924135

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

    PubMed

    Gupta, Abhishek; Myrdal, Paul B

    2004-04-01

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

  10. How to Use Metered-Dose Inhalers

    MedlinePlus

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

  11. A correlation equation for the mass median aerodynamic diameter of the aerosol emitted by solution metered dose inhalers.

    PubMed

    Ivey, James W; Lewis, David; Church, Tanya; Finlay, Warren H; Vehring, Reinhard

    2014-04-25

    A correlation equation for the mass median aerodynamic diameter (MMAD) of the aerosol emitted by solution metered dose inhalers (MDIs) is presented. A content equivalent diameter is defined and used to describe aerosols generated by evaporating metered dose inhaler sprays. A large set of cascade impaction data is analyzed, and the MMAD and geometric standard deviation is calculated for each datum. Using dimensional analysis, the mass median content equivalent diameter is correlated with formulation variables. Based on this correlation in combination with mass balance considerations and the definition of the aerodynamic diameter, an equation for prediction of the MMAD of an inhaler given the pressure of the propellant in the metering chamber of the MDI valve and the surface tension of the propellant is derived. The accuracy of the correlation equation is verified by comparison with literature results. The equation is applicable to both HFA (hydrofluoroalkane) propellants 134a and 227ea, with varying levels of co-solvent ethanol. PMID:24524827

  12. The Effect of Spacer Morphology on the Aerosolization Performance of Metered-Dose Inhalers

    PubMed Central

    Momeni, Sepideh; Nokhodchi, Ali; Ghanbarzadeh, Saeed; Hamishehkar, Hamed

    2016-01-01

    Purpose: Respiratory drug delivery has been attracted great interest for the past decades, because of the high incidence of pulmonary diseases. However, despite its invaluable benefits, there are some major drawbacks in respiratory drug delivery, mainly due to the relatively high drug deposition in undesirable regions. One way to improve the efficiency of respiratory drug delivery through metered-dose inhalers (MDI) is placing a respiratory spacer between the inhaler exit and the mouth. The aim of this study was to assess the effect of type and shape of spacer on the aerosolization performance of MDIs. Methods: A commercial Beclomethasone Dipropionate (BDP) MDI alone or equipped with two different spacer devices (roller and pear type) widely distributed in the world pharmaceutical market was used. The effect of spacers was evaluated by calculating aerosolization indexes such as fine particle fraction (FPF), mass median aerodynamic diameters (MMAD) and geometric standard deviation (GSD) using the next generation impactor. Results: Although one of the spacers resulted in superior outcomes than the other one, but it was not statistically significant. Conclusion: The results confirmed that the type and shape of spacer did not substantially influence the aerosolization performance of MDIs. PMID:27478789

  13. The Evolution of Pressurized Metered-Dose Inhalers from Early to Modern Devices.

    PubMed

    Roche, Nicolas; Dekhuijzen, P N Richard

    2016-08-01

    Pressurized metered-dose inhalers (pMDIs) are sometimes viewed as old-fashioned and as having been superseded by dry powder inhalers (DPIs). Here, we review the technological advances that characterize modern pMDIs, and consider how they can influence the effectiveness of drug delivery for patients with asthma and chronic obstructive pulmonary disease. Compared with old chlorofluorocarbon (CFC)-based inhalers, many hydrofluoroalkane (HFA)-driven pMDIs have more favorable plume characteristics such as a reduced velocity and a higher fine particle fraction; together, these advances have resulted in the development of pMDIs with reduced oropharyngeal deposition and increased lung deposition. In addition, the plume from many HFA-pMDIs is warmer, which may facilitate their use by patients; moreover, devices are equipped with dose counters, which improves their reliability. As well as reviewing the technological advances of pMDIs, we also discuss the importance of individualizing inhaler therapies to each patient by accounting for their personal preferences and natural breathing patterns. Because pMDIs and DPIs differ considerably in their handling characteristics, matching the right inhaler to the right patient is key to ensuring effective therapy and good compliance. Finally, the majority of patients can be trained successfully in the correct use of their pMDI; training and regular monitoring of inhalation technique are essential prerequisites for effective therapy. While the 'ideal inhaler' may not exist, pMDIs are an effective device option suitable for many patients. pMDIs, together with other types of devices, offer opportunities for the effective individualization of treatments. PMID:26824873

  14. Sildenafil citrate monohydrate-cyclodextrin nanosuspension complexes for use in metered-dose inhalers.

    PubMed

    Sawatdee, Somchai; Phetmung, Hirihattaya; Srichana, Teerapol

    2013-10-15

    Sildenafil is a selective phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. Sildenafil citrate monohydrate was complexed with α-, hydroxypropyl-β- and γ-cyclodextrin (α-CD, HP-β-CD and γ-CD, respectively) to enhance its water solubility. The complexes of sildenafil citrate monohydrate with all types of CDs were characterized by phase solubility diagrams, (1)H and (13)C NMR, and dielectric constants. Sildenafil citrate monohydrate complexed with CDs was developed as nanosuspensions for use in a pressurized metered-dose inhaler (pMDI). Sildenafil citrate monohydrate pMDI formulations were prepared by a bottom-up process using dried ethanol as a solvent and HFA-134a as an antisolvent and propellant in order to form nanosuspensions. A 3×3 factorial design was applied for the contents of the dried ethanol and HFA-134a propellant. The phase solubility profiles of the sildenafil and cyclodextrins were described as AL type with a mole ratio 1:1. The piperazine moiety of sildenafil formed an inclusion in the cavity of the CDs. The particle diameters of the sildenafil citrate monohydrate suspensions in pMDIs were all within a nanosuspension size range. An assay of the sildenafil content showed that the formation of complexes with CDs was close to 100%. In the case of the formulations with CDs, the emitted doses varied within 97.4±10.8%, the fine particle fractions (FPFs) were in a range of 45-81%, the fine particle dose (FPD) was 12.6±2.0 μg and the mass median aerodynamic diameters (MMADs) were 1.86±0.41 μm. In contrast, the formulations without CDs produced a low emitted dose of sildenafil (<60%). Therefore, only sildenafil citrate monohydrate pMDI formulations containing CDs were suitable for use as aerosols. PMID:23876498

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

    PubMed

    Sritara, P; Janvitayanuchit, S

    1993-12-01

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

  16. Evaluation of sildenafil pressurized metered dose inhalers as a vasodilator in umbilical blood vessels of chicken egg embryos.

    PubMed

    Sawatdee, Somchai; Hiranphan, Phetai; Laphanayos, Kampanart; Srichana, Teerapol

    2014-01-01

    Sildenafil citrate is a selective phosphodiesterase-5 inhibitor used for the treatment for erectile dysfunction and pulmonary hypertension. The delivery of sildenafil directly to the lung could have several advantages over conventional treatments for pulmonary hypertension because of the local delivery, a more rapid onset of response, and reduced side effects. The major problem of sildenafil citrate is its limited solubility in water. Sildenafil citrate was complexed with cyclodextrins (CDs) to enhance its water solubility prior to development as an inhaled preparation. Four sildenafil citrate inhaled formulations were prepared with the aid of HP-β-CD (#1), α-CD (#2) and γ-CD (#3) and their effects were compared with the formulations without CDs (#4). The sildenafil citrate pressurized metered dose inhalers (pMDI) used ethanol as a solvent, PEG400 as a stabilizing agent, sorbitan monooleate as a surfactant and HFA-134a as a propellant. All formulations consisted of sildenafil citrate equivalent to a sildenafil content of 20μg/puff. These products were evaluated according to a standard guideline of inhalation products. Vasodilation testing was performed to investigate the efficacy of sildenafil pMDIs in relieving a vasoconstricted umbilical blood vessel of the chicken egg embryo. The sildenafil contents of the pMDI formulations #1-#3 were within the acceptance criteria (80-120%). The emitted doses (ED) were 102.3±11.5%, the fine particle fractions (FPF) were 60.5±5.6% and the mass median aerodynamic diameters (MMAD) were 2.3±0.3μm. The vasodilatory activity of those formulations reduced umbilical blood pressure by 67.1-73.7% after treatment by intravenous injection whereas only a 50.1-58.0% reduced blood pressure was obtained after direct spraying of the sildenafil pMDI containing CDs. With sildenafil formulations of a pMDI without CD the blood pressure was reduced by only 39.0% (P-value<0.05). The available sildenafil in the blood vessels of chicken egg

  17. Therapeutic comparison of a new budesonide/formoterol pMDI with budesonide pMDI and budesonide/formoterol DPI in asthma

    PubMed Central

    Morice, A H; Peterson, S; Beckman, O; Osmanliev, D

    2007-01-01

    Background Budesonide/formoterol is an effective treatment for both asthma and chronic obstructive pulmonary disease. This study compared the efficacy and safety of a novel hydrofluoroalkane (HFA) pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol with that of budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI; Turbuhaler®). Methods This was a 12-week, multinational, randomised, double-blind, double-dummy study involving patients aged ≥ 12 years with asthma. All patients had a forced expiratory volume in 1 s of 50–90% predicted normal and were inadequately controlled on inhaled corticosteroids (500–1600 mu g/day) alone. Following a 2-week run-in, during which they received their usual medication, patients were randomised (two inhalations twice daily) to budesonide pMDI 200 mu g, budesonide/formoterol DPI 160/4.5 mu g or budesonide/formoterol pMDI 160/4.5 mu g. The primary efficacy end-point was change from baseline in morning peak expiratory flow (PEF). Results In total, 680 patients were randomised, of whom 668 were included in the primary analysis. Therapeutically equivalent increases in morning PEF were observed with budesonide/formoterol pMDI (29.3 l/min) and budesonide/formoterol DPI (32.0 l/min) (95% confidence interval: −10.4 to 4.9; p = 0.48). The increase in morning PEF with budesonide/formoterol pMDI was significantly higher than with budesonide pMDI (+28.7 l/min; p < 0.001). Similar improvements with budesonide/formoterol pMDI vs. budesonide pMDI were seen for all secondary efficacy end-points. Both combination treatments were similarly well tolerated. Conclusions Budesonide/formoterol, administered via the HFA pMDI or DPI, is an effective and well-tolerated treatment for adult and adolescent patients with asthma, with both devices being therapeutically equivalent. PMID:17887990

  18. Dose to lung from inhaled tritiated particles.

    PubMed

    Richardson, R B; Hong, A

    2001-09-01

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

  19. Comparison of gamma scintigraphy and a pharmacokinetic technique for assessing pulmonary deposition of terbutaline sulphate delivered by pressurized metered dose inhaler.

    PubMed

    Newman, S; Steed, K; Hooper, G; Källén, A; Borgström, L

    1995-02-01

    A comparison has been made of pulmonary deposition of terbutaline sulphate from a pressurized metered dose inhaler (pMDI), measured in 8 healthy male subjects by gamma scintigraphy and by a pharmacokinetic (charcoal-block) method, involving drug recovery in urine. Measurements were carried out with a pMDI at slow (27 l/min) and fast (151 l/min) inhaled flows and with Nebuhaler large volume spacer device (average inhaled flow 17 l/min). Overall, the two methods did not differ significantly in their estimates of whole lung deposition, although values obtained by gamma scintigraphy exceeded those from the charcoal-block method for the pMDI with fast inhalation. The regional distribution of drug within the lungs and deposition in the oropharynx could be assessed by gamma scintigraphy, but not by the charcoal-block method. It is concluded that either method may be used to assess whole lung deposition of terbutaline sulphate from pMDIs, both with and without a spacer, although each method has its own inherent advantages and disadvantages. PMID:7784338

  20. Establishing a Quality Control Program: Ensuring Safety From Contamination for Recycled Metered-Dose Inhalers

    PubMed Central

    Clyne, Kurt; Knapp, Donnet; Snyder, Jay

    2014-01-01

    Abstract Background: Recycling metered-dose inhalers (MDIs) is an effective method to conserve medications resulting in significant cost savings to the hospital. A noted limitation in some reports is the potential for cross-contamination. Objective: To implement a quality control program to monitor and validate the safety of recycled MDIs for institutional reuse. Methods: A quality control program was conducted from December 2012 to May 2013. At a 257-bed acute care facility, MDIs are administered to a single patient using a patient-specific valved holding chamber and then returned to the pharmacy for cleaning with 70% isopropyl alcohol prior to re-dispensing to a new patient. Ten percent of MDIs from 3 categories were categorized: prior to pharmacy cleaning, after pharmacy cleaning, and new/unused control group each month. The mouthpiece and canister spray tip from each MDI were tested. Any bacterial growth was documented. A secondary test was conducted to ensure that artificially contaminated MDIs could be cleaned with current cleaning procedures. Cost savings measures were also quantified. Results: There was no bacterial growth on the 17 recycled MDIs cultured prior to the cleaning process. Bacteria did not grow on any of the 33 recycled MDIs cleaned with 70% isopropyl alcohol. Likewise, in the control group of 33 new/unused control MDIs, there was no bacterial growth. No bacteria growth was found after cleaning each artificially contaminated MDI. Total drug cost savings during the study period was approximately $130,000. Conclusions: Establishing a strict quality control program is paramount to validating a safe and effective recycled MDI procedure. PMID:24958955

  1. Factors affecting the stability and performance of ipratropium bromide; fenoterol hydrobromide pressurized-metered dose inhalers.

    PubMed

    Ninbovorl, Jenjira; Sawatdee, Somchai; Srichana, Teerapol

    2013-12-01

    The aim of the study was to investigate the factors affecting the stability and performance of ipratropium bromide and fenoterol hydrobromide in a pressurized-metered dose inhaler (pMDI). A factorial design was applied to investigate the effects of three parameters (propellant, water, and ethanol) on the performance of 27 designed formulations of a solution-based pMDI. The formulations that contained a hydrofluoroalkane (HFA) propellant lower than 72% v/v and an ethanol concentration higher than 27% v/v remained as clear solutions. Nine formulations that contained the HFA propellant higher than 74% v/v precipitated. The results indicated that it was not only the HFA propellant content of the formulations that was related to the formulation instability but also ethanol content. Only six formulations from the 18 formulations, that did not precipitate, produced drug contents that were within the acceptable range (80-120%). These six formulations generated aerosols with mass median aerodynamic diameters (MMAD) of approximately 2 μm with a fine particle fraction (FPF; particle size, <6.4 μm) between 45% and 52%. The MMAD and FPF did not change significantly after 6 months of storage (P > 0.05). PMID:23975571

  2. Tuning Aerosol Particle Size Distribution of Metered Dose Inhalers Using Cosolvents and Surfactants

    PubMed Central

    Saleem, Imran Y.; Smyth, Hugh D. C.

    2013-01-01

    Objectives. The purpose of these studies was to understand the influence of cosolvent and surfactant contributions to particle size distributions emitted from solution metered dose inhalers (pMDIs) based on the propellant HFA 227. Methods. Two sets of formulations were prepared: (a) pMDIs-HFA 227 containing cosolvent (5–15% w/w ethanol) with constant surfactant (pluronic) concentration and (b) pMDIs-HFA 227 containing surfactant (0–5.45% w/w pluronic) with constant cosolvent concentration. Particle size distributions emitted from these pMDIs were analyzed using aerodynamic characterization (inertial impaction) and laser diffraction methods. Results. Both cosolvent and surfactant concentrations were positively correlated with median particle sizes; that is, drug particle size increased with increasing ethanol and pluronic concentrations. However, evaluation of particle size distributions showed that cosolvent caused reduction in the fine particle mode magnitude while the surfactant caused a shift in the mode position. These findings highlight the different mechanisms by which these components influence droplet formation and demonstrate the ability to utilize the different effects in formulations of pMDI-HFA 227 for independently modulating particle sizes in the respirable region. Conclusion. Potentially, the formulation design window generated using these excipients in combination could be used to match the particle size output of reformulated products to preexisting pMDI products. PMID:23984381

  3. Efficacy and safety of ipratropium bromide/salbutamol sulphate administered in a hydrofluoroalkane metered-dose inhaler for the treatment of COPD

    PubMed Central

    Bhattacharya, Amal; Bhargava, Salil; Singh, Virendra; Talwar, Deepak; Whig, Jagdeep; Rebello, Juliet; Purandare, Shrinivas; Gogtay, Jaideep

    2016-01-01

    Background The use of chlorofluorocarbons (CFCs) has contributed to the depletion of the stratospheric ozone layer resulting in serious health concerns. Ipratropium bromide/salbutamol sulphate CFC-pressurized metered-dose inhalers (IB/SAL-CFC pMDI) have been in widespread use for many years without any apparent ill consequences. This combination has now been reformulated using the hydrofluoroalkane (HFA) propellant. This study sought to establish the clinical noninferiority of a new HFA-containing IB/SAL pMDI to the conventional IB/SAL-CFC pMDI in subjects with mild/moderate COPD. Methods This was a randomized, double-blind, parallel-group, multicenter study in two consecutive periods: a 14-day run-in period followed by a 85-day treatment period. Eligible mild-to-moderate stable COPD subjects aged 40−75 years were enrolled into the study and entered the run-in period during which subjects withdrew all the bronchodilators, except for salbutamol as rescue medication. Subjects were randomized to 85 days treatment with either IB/SAL-HFA or IB/SAL-CFC, 20 μg qid. Results Of the 290 randomized patients, 249 completed the study. The primary efficacy variable was the change in forced expiratory volume in one second from predose to 60 minutes after dosing on day 85. At the end of the treatment period, the adjusted mean change in forced expiratory volume in one second at 60 minutes was 123 mL in the IB/SAL-HFA pMDI group and 115 mL in the IB/SAL-CFC pMDI group. Because the lower limit of the 95% confidence interval for the between-group difference (−62 mL) was well within the noninferiority margin (−100 mL), the HFA formulation was deemed clinically noninferior to the CFC formulation. This finding was supported by secondary efficacy assessments. Both formulations of IB/SAL were well tolerated during the prolonged multiple dosing. Conclusion It is concluded that IB/SAL-HFA pMDI provides effective bronchodilation of similar degree to that achieved with IB/SAL-CFC pMDI

  4. Stability and aerosolization of pressurized metered dose inhalers containing thymopentin nanoparticles produced using a bottom-up process.

    PubMed

    Tan, Yinhe; Yang, Zhiwen; Pan, Xin; Chen, Meiwan; Feng, Min; Wang, Lili; Liu, Hu; Shan, Ziyun; Wu, Chuanbin

    2012-05-10

    The objective of this study was to investigate the stability and aerosolization of pressurized metered dose inhalers (pMDIs) containing thymopentin nanoparticles. Thymopentin nanoparticles, fabricated by a bottom-up process, were suspended in hydrofluoroalkane (HFA) 134a together with cineole and/or n-heptane to produce pMDI formulations. The stability study of the pMDIs obtained was carried out at ambient temperature for 6 months. The amount of thymopentin and the aerosolization properties of pMDIs were determined using high-performance liquid chromatography (HPLC) and a twin-stage impinger (TSI), respectively. Based on the results, thymopentin nanoparticles were readily suspended in HFA 134a with the aid of cineole and/or n-heptane to form physically stable pMDI formulations, and more than 98% of the labeled amount of thymopentin and over 50% of the fine particle fraction (FPF) of the pMDIs were achieved. During storage, it was found that for all pMDIs more than 97% of the labeled amount of thymopentin and FPF greater than 47% were achieved. Moreover, the size of thymopentin nanoparticles in propellant containing cineole and n-heptane showed little change. It is, therefore, concluded that the pMDIs comprising thymopentin nanoparticles developed in this study were stable and suitable for inhalation therapy for systemic action. PMID:22343132

  5. Evaluation of metered dose inhaler spray velocities using phase Doppler anemometry (PDA).

    PubMed

    Liu, Xiaofei; Doub, William H; Guo, Changning

    2012-02-28

    Droplet velocity is an important parameter which can significantly influence inhalation drug delivery performance. Together with the droplet size, this parameter determines the efficiency of the deposition of MDI products at different sites within the lungs. In this study, phase Doppler anemometry (PDA) was used to investigate the instantaneous droplet velocity emitted from MDIs as well as the corresponding droplet size distribution. The nine commercial MDI products surveyed showed significantly different droplet velocities, indicating that droplet velocity could be used as a discriminating parameter for in vitro testing of MDI products. The droplet velocity for all tested MDI products decreased when the testing distance was increased from 3 cm to 6 cm from the front of mouthpiece, with CFC formulations showing a larger decrease than HFA formulations. The mean droplet diameters of the nine MDIs were also significantly different from one-another. Droplet size measurements made using PDA (a number-based technique) could not be directly compared to results obtained using laser light scattering measurements (a volume-based technique). This work demonstrates that PDA can provide unique information useful for characterizing MDI aerosol plumes and evaluating MDI drug delivery efficiency. PDA could also aid the evaluation of in vitro equivalence in support of formulation or manufacturing changes and in evaluation of abbreviated new drug applications (ANDAs) for MDIs. PMID:22183132

  6. Airmax: a multi-dose dry powder inhaler.

    PubMed

    Keating, Gillian M; Faulds, Diana

    2002-01-01

    Airmax is a multi-dose dry powder inhaler. An internal pump measures out the drug dose using controlled air pressure. Inhalation transports the drug into a cyclone separator (where active drug is separated from the lactose carrier) and then into the patient airway. In vitro studies indicate that Airmax may be less dependent on airflow than Turbuhaler for drug delivery; greater dose consistency was seen with administration of budesonide via Airmax than via Turbuhaler. At a low flow rate, the lung deposition of budesonide administered via Airmax was greater than that of budesonide administered via Turbuhaler or a pressurised metered dose inhaler in patients with asthma. In cumulative-dose studies, the mean forced expiratory volume in 1 second (FEV(1)) achieved with salbutamol (albuterol) or formoterol administered via Airmax was equivalent to that achieved with twice the dose administered via dry powder inhalers. black triangle In randomised, double-blind studies, budesonide administration via Airmax was equivalent to administration via Turbuhaler with regards to FEV(1) and improvement in asthma symptoms in both adults and children with asthma. The concentration of adenosine monophosphate producing a 20% fall in FEV(1) increased from pretreatment levels by a greater extent with budesonide administered via Airmax, compared with Turbuhaler. Both adults and children preferred Airmax to Turbuhaler, and more found Airmax easier to use. In one study, the majority of children found learning how to use Airmax trade mark easier than learning how to use Turbuhaler. PMID:12215059

  7. 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.

    PubMed

    Eisenberg, Elon; Ogintz, Miri; Almog, Shlomo

    2014-09-01

    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. PMID:25118789

  8. Moisture uptake and its influence on pressurized metered-dose inhalers.

    PubMed

    Williams, R O; Hu, C

    2000-01-01

    The objective of this study was to investigate moisture ingress into pressurized metered dose inhalers (pMDIs) containing hydrofluoroalkane (HFA) propellants and the consequences of this ingress. Moisture ingress into the pMDIs containing tetrafluoroethane (HFA 134a) or heptafluoropropane (HFA 227) was evaluated and modeled. The influence of water level in pMDIs on the stability of pMDIs containing triamicinolone acetonide (TAA) and beclomethasone dipropionate (BDP) in terms of particle growth, fine particle fraction, and drug solubility in the propellant system was evaluated using scanning electron microscopy, particle size analysis, single-stage impaction, and HPLC. The water level in HFA-containing pMDIs increased during storage and the process obeyed a diffusion model. HFA 134a had a greater tendency to take up moisture from the environment than did HFA 227. Unlike TAA, the propensity for particle growth of the suspended BDP in HFA propellants was significantly depressed by the increase in water level in the pMDIs. As a result, the fine particle fraction of the emitted BDP aerosols significantly increased as the water level in the HFA propellant was increased. Moisture ingress into pMDIs containing HFAs occurred during storage. The influence of the increased water level in pMDIs on the physical stability of the pMDI formulation and the dose delivery performance was a function of the composition of the internal lining of the container, the type of drug and propellant, and storage temperature. PMID:10810745

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

    PubMed

    Mitchell, Jolyon; Dolovich, Myrna B

    2012-08-01

    Regulatory guidance in Canada and Europe recommends that the manufacturer of an inhaled drug product delivered by pressurized metered-dose inhaler (pMDI) identify a spacer (S) or valved holding chamber (VHC) to be used with their designated product. It therefore becomes necessary to include the S/VHC in the process of establishing bioequivalence (BE) to the reference pMDI product for both new-entry generic and subsequent market entry products (SMEPs). S/VHCs substantially modify the aerodynamic particle size distribution (APSD) of the inhaled medication, and potentially the spatial distribution of the mass of active pharmaceutical ingredient(s) [API(s)] depositing in the respiratory tract. The processes whereby S/VHCs can influence BE outcomes are examined, and the inadequacy of compendial in vitro methods to provide pertinent information to assess BE for the pMDI+VHC combination is highlighted. A three-part strategy is proposed whereby in vitro testing for BE can simulate more clinically-relevant conditions than in the current compendial procedures: 1. The inclusion of a short delay between inhaler actuation and sampling onset is appropriate when determining APSD at flow rate(s) suitable for the intended patient population; 2. Assessment of total emitted mass ex S/VHC by simulating tidal breathing pattern(s) appropriate for intended use; 3. Incorporation of appropriate face model(s), representative of the intended patient age range(s), into test procedures for S/VHCs with facemask, enabling clinically-appropriate dead space and fit-to-face to be simulated. Although the compendial authorities have been slow to recognize the need for such in vitro testing, a Canadian standard provides direction for implementing most proposals, which should result in better performance predictions and more appropriate clinical outcomes, highlighting similarities and differences between reference and test products. PMID:22857273

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

    PubMed Central

    Daley-Yates, Peter T

    2015-01-01

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

  11. Pulmonary carcinogenicity of inhaled particles and the maximum tolerated dose.

    PubMed Central

    Oberdörster, G

    1997-01-01

    Chronic inhalation bioassays in rodents are used to assess pulmonary carcinogenicity for purposes of hazard identification and potentially for risk characterization. The influence of high experimental doses on tumor development has been recognized for some time and has led to the concept of maximum tolerated dose (MTD) for dose selection, with the highest dose being at the MTD. Exposure at the MTD should ensure that the animals are sufficiently challenged while at the same time the animal's normal longevity is not altered from effects other than carcinogenicity. A characteristic of exposure-dose-response relationships for chronically inhaled particles is that lung tumors are significantly increased only at high exposure levels, and that lung tumors are seen in rats only but not in mice or hamsters. This lung tumor response in rats is thought to be secondary to persistent alveolar inflammation, indicating that the MTD may have been exceeded. Thus, mechanisms of toxicity and carcinogenicity may be dose dependent and may not operate at lower doses that humans normally experience. Despite awareness of this problem, carcinogenicity bioassays that evaluate particulate compounds in rodents have not always been designed with the MTD concept in mind. This is due to several problems associated with determining an appropriate MTD for particle inhalation studies. One requirement for the MTD is that some toxicity should be observed. However, it is difficult to define what degree of toxic response is indicative of the MTD. For particle inhalation studies, various noncancer end points in addition to mortality and body weight gain have been considered as indicators of the MTD, i.e., pulmonary inflammation, increased epithelial cell proliferation, increased lung weight, impairment of particle clearance function, and significant histopathological findings at the end of a subchronic study. However, there is no general agreement about quantification of these end points to define the

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

    PubMed

    Persson, G; Gruvstad, E; Ståhl, E

    1988-08-01

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

  13. The application of "in-flight" laser diffraction to the particle size characterization of a model suspension metered dose inhaler.

    PubMed

    Pu, Yu; Kline, Lukeysha C; Berry, Julianne

    2011-05-01

    Laser diffraction (LD) has been used to measure the particle size of pharmaceutical aerosols. In this study, the application of LD for measuring the particle size of a model suspension metered dose inhaler (MDI) containing a hydrofluorocarbon propellant was investigated using a Sympatec LD apparatus with an automatic spray device. In order to obtain meaningful results, test parameters such as spray distance and temperature needed to be optimized for this model formulation and then well-controlled during testing. Using a suitable LD test methodology, it was found that particle size variations as a function of nonvolatile excipient levels as well as changes to the suspended drug substance could be observed and, in some cases, correlated to cascade impaction results. Based on these studies, it is believed that the methodology is a valuable rapid screening tool for investigating variations in or permutations to suspension MDI formulations. Nonetheless, the trends in the LD droplet size are complicated by the presence of drug-free droplets. Consequently, the results are not always consistent with other particle sizing techniques such as cascade impaction in which the droplets associated with drug are evaluated. Therefore, for suspension MDIs, the "in-flight" LD method would probably best be utilized as a complementary sizing technique during formulation development. PMID:21126224

  14. Factors influencing aerodynamic particle size distribution of suspension pressurized metered dose inhalers.

    PubMed

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

    2015-02-01

    Pressurized metered dose inhalers (pMDIs) are frequently used for the treatment of asthma and chronic obstructive pulmonary disease. The aerodynamic particle size distribution (APSD) of the residual particles delivered from a pMDI plays a key role in determining the amount and region of drug deposition in the lung and thereby the efficacy of the inhaler. In this study, a simulation model that predicts the APSD of residual particles from suspension pMDIs was utilized to identify the primary determinants for APSD. These findings were then applied to better understand the effect of changing drug concentration and micronized drug size on experimentally observed APSDs determined through Andersen Cascade Impactor testing. The experimental formulations evaluated had micronized drug mass median aerodynamic diameters (MMAD) between 1.2 and 2.6 μm and drug concentrations ranging from 0.01 to 1% (w/w) with 8.5% (w/w) ethanol in 1,1,1,2-tetrafluoroethane (HFA-134a). It was determined that the drug concentration, micronized drug size, and initially atomized droplet distribution have a significant impact in modulating the proportion of atomized droplets that contain multiple suspended drug particles, which in turn increases the residual APSD. These factors were found to be predictive of the residual particle MMAD for experimental suspension HFA-134a formulations containing ethanol. The empirical algebraic model allows predicting the residual particle size for a variety of suspension formulations with an average error of 0.096 μm (standard deviation of 0.1 μm). PMID:25273026

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

    PubMed

    Abdelrahim, Mohamed E

    2010-05-01

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

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

    PubMed

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

    2014-01-01

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

  17. The inhalation device influences lung deposition and bronchodilating effect of terbutaline.

    PubMed

    Borgström, L; Derom, E; Ståhl, E; Wåhlin-Boll, E; Pauwels, R

    1996-05-01

    The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect. PMID:8630614

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

    PubMed Central

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

    2015-01-01

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

  19. Moisture transport into chlorofluorocarbon-free metered dose inhalers.

    PubMed

    Williams, G

    1999-12-01

    Moisture is known to affect the stability of some metered dose inhalers (MDIs). Hydrofluoroalkanes such as tetrafluoroethane (134a) and heptafluoropropane (227) are known to have higher affinity for moisture than the currently used chlorofluorocarbon propellents. An initial study was conducted to determine the water vapor transmission rates of various elastomers that may be used as gaskets in MDIs. A further study was conducted to measure the moisture ingress rates of various chlorofluorocarbon-free MDIs. The data indicate that moisture transport into chlorofluorocarbon-free MDIs is influenced by the elastomeric nature of the gaskets used and the type of hydrofluoroalkane formulation and storage conditions used. PMID:10588979

  20. Towards the bioequivalence of pressurised metered dose inhalers 1: design and characterisation of aerodynamically equivalent beclomethasone dipropionate inhalers with and without glycerol as a non-volatile excipient.

    PubMed

    Lewis, D A; Young, P M; Buttini, F; Church, T; Colombo, P; Forbes, B; Haghi, M; Johnson, R; O'Shea, H; Salama, R; Traini, D

    2014-01-01

    A series of semi-empirical equations were utilised to design two solution based pressurised metered dose inhaler (pMDI) formulations, with equivalent aerosol performance but different physicochemical properties. Both inhaler formulations contained the drug, beclomethasone dipropionate (BDP), a volatile mixture of ethanol co-solvent and propellant (hydrofluoroalkane-HFA). However, one formulation was designed such that the emitted aerosol particles contained BDP and glycerol, a common inhalation particle modifying excipient, in a 1:1 mass ratio. By modifying the formulation parameters, including actuator orifice, HFA and metering volumes, it was possible to produce two formulations (glycerol-free and glycerol-containing) which had identical mass median aerodynamic diameters (2.4μm±0.1 and 2.5μm±0.2), fine particle dose (⩽5μm; 66μg±6 and 68μg±2) and fine particle fractions (28%±2% and 30%±1%), respectively. These observations demonstrate that it is possible to engineer formulations that generate aerosol particles with very different compositions to have similar emitted dose and in vitro deposition profiles, thus making them equivalent in terms of aerosol performance. Analysis of the physicochemical properties of each formulation identified significant differences in terms of morphology, thermal properties and drug dissolution of emitted particles. The particles produced from both formulations were amorphous; however, the formulation containing glycerol generated particles with a porous structure, while the glycerol-free formulation generated particles with a primarily spherical morphology. Furthermore, the glycerol-containing particles had a significantly lower dissolution rate (7.8%±2.1%, over 180min) compared to the glycerol-free particles (58.0%±2.9%, over 60min) when measured using a Franz diffusion cell. It is hypothesised that the presence of glycerol in the emitted aerosol particles altered solubility and drug transport, which may have

  1. Saharan dust levels in Greece and received inhalation doses

    NASA Astrophysics Data System (ADS)

    Mitsakou, C.; Kallos, G.; Papantoniou, N.; Spyrou, C.; Solomos, S.; Astitha, M.; Housiadas, C.

    2008-06-01

    The desert of Sahara is one of the major sources of mineral dust on Earth, producing around 2×108 tons/yr. Under certain weather conditions, dust particles from Saharan desert get transported over the Mediterranean Sea and most of Europe. The limiting values set by the directive EC/30/1999 of European Union can easily be exceeded by the transport of desert dust particles in all south European areas and especially urban. In this study, the effects of dust transport on air quality in several Greek urban areas are quantified. PM10 concentration values from stationary monitoring stations are compared to dust concentrations for the 4-year period 2003-2006. The dust concentration values in the Greek areas were estimated by the SKIRON modelling system coupled with embedded algorithms describing the dust cycle. The mean annual dust contribution to daily-averaged PM10 concentration values was found to be around or even greater than 10% in the urban areas throughout the years examined. Natural dust transport may contribute by much more than 20% to the annual number of exceedances - PM10 values greater than EU limits - depending on the specific monitoring location. In a second stage of the study, the inhaled lung dose received by the residents in various Greek locations is calculated. The particle deposition efficiency of mineral dust at the different parts of the human respiratory tract is determined by applying a lung dosimetry numerical model, which incorporates inhalation dynamics and aerosol physical processes. The inhalation dose from mineral dust particles was greater in the upper respiratory system (extrathoracic region) and less significant in the lungs, especially in the sensitive alveolar region. However, in cases of dust episodes, the amounts of mineral dust deposited along the human lung are comparable to those received during exposure in heavily polluted urban or smoking areas.

  2. Saharan dust levels in Greece and received inhalation doses

    NASA Astrophysics Data System (ADS)

    Mitsakou, C.; Kallos, G.; Papantoniou, N.; Spyrou, C.; Solomos, S.; Astitha, M.; Housiadas, C.

    2008-12-01

    The desert of Sahara is one of the major sources of mineral dust on Earth, producing around 2×108 tons/yr. Under certain weather conditions, dust particles from Saharan desert get transported over the Mediterranean Sea and most of Europe. The limiting values set by the directive EC/30/1999 of European Union can easily be exceeded by the transport of desert dust particles in the south European Region and especially in urban areas, where there is also significant contribution from anthropogenic sources. In this study, the effects of dust transport on air quality in several Greek urban areas are quantified. PM10 concentration values from stationary monitoring stations are compared to dust concentrations for the 4-year period 2003-2006. The dust concentration values in the Greek areas were estimated by the SKIRON modelling system coupled with embedded algorithms describing the dust cycle. The mean annual dust contribution to daily-averaged PM10 concentration values was found to be around or even greater than 10% in the urban areas throughout the years examined. Natural dust transport may contribute by more than 20% to the annual number of exceedances - PM10 values greater than EU limits - depending on the specific monitoring location. In a second stage of the study, the inhaled lung dose received by the residents in various Greek locations is calculated. The particle deposition efficiency of mineral dust at the different parts of the human respiratory tract is determined by applying a lung dosimetry numerical model, which incorporates inhalation dynamics and aerosol physical processes. The inhalation dose from mineral dust particles was greater in the upper respiratory system (extrathoracic region) and less significant in the lungs, especially in the sensitive alveolar region. However, in cases of dust episodes, the amounts of mineral dust deposited along the human lung are comparable to those received during exposure in heavily polluted urban or smoking areas.

  3. Mucolytic treatment with N-acetylcysteine L-lysinate metered dose inhaler in dogs: airway epithelial function changes.

    PubMed

    Tomkiewicz, R P; App, E M; Coffiner, M; Fossion, J; Maes, P; King, M

    1994-01-01

    N-acetylcysteine L-lysinate Nacystelyn (L-NAC) is a newly synthesized mucolytic agent, of which the action in vivo has not been well defined. In six healthy mongrel dogs, the rheological properties of mucus, its mucociliary and cough clearability, and the transepithelial potential difference (PD) of the tracheobronchial epithelium were evaluated after placebo and L-NAC metered dose inhaler (MDI) aerosols. The principal index of mucus rigidity, log G*, decreased at all airway sites with L-NAC administration, i.e. the mucus became less rigid and more deformable (the overall change in G* was 0.29 log units, i.e. ca. twofold decrease). The viscoelasticity-derived mucus transportability parameters, mucociliary (MCI) and cough (CCI) clearability indices, increased with L-NAC MDI, particularly CCI, which predicts the effect of mucus rheology on cough clearability. PD increased significantly with L-NAC administration at all measurement sites, which appears to be a novel effect for a direct acting mucolytic agent. Tracheal mucus linear velocity (TMV) increased after L-NAC compared with placebo, as did the normalized frog palate transport rate (NFPTR). The increase in NFPTR was greater than that predicted from the mucus rheological properties alone, suggesting that L-NAC still resident in the collected mucus stimulated the frog palate cilia. The index of mucus flux, the collection rate in mg.min-1, was higher with L-NAC compared with placebo. From our results, we conclude that L-NAC shows potential benefit in terms of improving mucus rheological properties and clearability. It may act, in part, by stimulating the fresh secretion of mucus of lower viscoelasticity. The stimulation of mucociliary clearance could be related to ion flux changes, as indicated by the increase in PD. PMID:8143836

  4. Dose emission and aerodynamic characterization of the terbutaline sulphate dose emitted from a Turbuhaler at low inhalation flow.

    PubMed

    Abdelrahim, M E; Assi, K H; Chrystyn, H

    2013-01-01

    Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa. PMID:21981637

  5. Inhalants

    MedlinePlus

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

  6. Pharmacokinetics and pharmacodynamics of an extrafine fixed pMDI combination of beclometasone dipropionate/formoterol fumarate in adolescent asthma

    PubMed Central

    Kuna, Piotr; Govoni, Mirco; Lucci, Germano; Scuri, Mario; Acerbi, Daniela; Stelmach, Iwona

    2015-01-01

    Aim The aim was to investigate the pharmacokinetics and pharmacodynamics of an extrafine pressurized metered-dose inhaler (pMDI) fixed combination of beclometasone dipropionate (BDP)/formoterol fumarate (FF) in adolescent and adult asthma. Methods This was a three-way crossover study, on 30 asthmatic adolescents receiving BDP/FF pMDI with or without a valved holding chamber (VHC) or a free licenced combination of BDP pMDI and FF pMDI plus a parallel arm of 30 asthmatic adults receiving BDP/FF pMDI. All patients received a single dose of BDP and FF of 400 µg and 24 µg, for each treatment, respectively. Assessments were performed over 8 hours. Results In adolescents, the 90% confidence intervals (CIs) for the systemic exposure (AUC(0,t)) geometric mean ratio of the fixed combination with or without VHC vs. the free combination were within the bioequivalence range 0.80–1.25, both for beclometasone-17-monopropionate (B17MP, the active metabolite of BDP) and formoterol. Pharmacodynamic variables for plasma potassium and glucose, pulse rate and pulmonary function in adolescents were equivalent between treatments, 95% CI within 0.9, 1.09. The upper level of 90% CIs for AUC(0,t) geometric mean ratio adolescents : adults of B17MP and formoterol after treatment with BDP/FF pMDI was lower than 1.25, 90% CI 0.78, 1.04 and 0.86, 1.17, respectively. Conclusions In adolescents the pharmacodynamics and the overall systemic exposure to the active ingredients of an extrafine fixed combination of BDP/FF pMDI with or without a VHC was equivalent to that of a free licenced combination of pMDIs of established safety and efficacy profiles. The systemic exposure in adolescents was not higher than in adults. These results support the indication for use of inhaled corticosteroid/long acting β2-adrenoceptor agonist pMDIs in adolescents at the same dosage as in adults. PMID:25808292

  7. Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurised metered dose inhaler, as a dry powder, and as a nebulised solution.

    PubMed Central

    Zainudin, B M; Biddiscombe, M; Tolfree, S E; Short, M; Spiro, S G

    1990-01-01

    The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution. Images PMID:2392793

  8. Methylene Diphenyl Diisocyanate (monomeric MDI) and polymeric MDI (PMDI)

    Integrated Risk Information System (IRIS)

    Methylene Diphenyl Diisocyanate ( monomeric MDI ) and polymeric MDI ( PMDI ) ; CASRN 101 - 68 - 8 , 9016 - 87 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment devel

  9. Bone mineral density in asthmatic patients using low dose inhaled glucocorticosteroids.

    PubMed

    El, O; Gulbahar, S; Ceylan, E; Ergor, G; Sahin, E; Senocak, O; Oncel, S; Cimrin, A

    2005-01-01

    Inhaled glucocorticosteroids are clearly beneficial in subjects with moderate or severe asthma since they are well tolerated, reduce symptoms, and improve quality of life. Some studies suggest that inhaled glucocorticosteroids can adversely affect bone mineral density. The aim of this study is to determine the effects of inhaled glucocorticosteroid therapy on bone mineral density in female patients. Forty-five asthmatic female patients (36 premenopousal and 9 postmenopausal) and forty-six healthy control subjects were included in the study. Bone mineral density was measured from lumbar spine (L1-4) and femur (neck, trochanter, and Ward's triangle) by dual energy X-Ray absorptiometry. Age, occupation, menopause and smoking status, alcohol consumption, body mass index, previous fractures, family history of fractures, menstrual history, ooferectomy, number of pregnancies, the duration of lactation, physical activity and calcium intake were questioned according to the European Vertebral Osteoporosis Study Group (EVOS) form. Cumulative inhaled glucocorticosteroid dose was calculated. T score of femoral neck and T score and bone mineral density of Ward's triangle were significantly lower in asthmatic patients compared to control group but no statistically significant correlation was found between the disease duration, inhaled steroid treatment duration, cumulative inhaled dose and annual inhaled steroid dose and bone mineral density measurement. These results suggest that in asthmatic patients using low dose inhaled corticosteroids bone mineral density is lower than in healthy controls but it is still unclear if asthma by itself is a risk factor for osteoporosis. PMID:15864884

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

    EPA Science Inventory

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

  11. Inhalants

    MedlinePlus

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

  12. Analysis of Exposure-Dose Variation of Inhaled Particles in Adult Subjects.

    EPA Science Inventory

    Although internal dose is a key factor for determining the health risk of inhaled pollutant particles, available dose information is largely limited to young healthy adults under a few typical exposure conditions. Extrapolation of the limited dose information to different populat...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2004-01-01

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

  15. Historical cohort study examining comparative effectiveness of albuterol inhalers with and without integrated dose counter for patients with asthma or chronic obstructive pulmonary disease

    PubMed Central

    Price, David B; Rigazio, Anna; Buatti Small, Mary; Ferro, Thomas J

    2016-01-01

    Background Using a metered-dose inhaler (MDI) beyond the labeled number of actuations may result in inadequate dosing of medication, which can lead to poor clinical outcomes. This study compared respiratory-related emergency department (ED) visit rates in patients with asthma, chronic obstructive pulmonary disease, or both when they used albuterol MDIs with versus without dose counters. Methods This retrospective study used US claims data to identify patients (ages 4–64 years) with asthma, chronic obstructive pulmonary disease, or both, using albuterol MDIs with or without an integrated dose counter. The study comprised a 1-year baseline period for patient characterization and confounder definition and a 1-year outcome period following the first albuterol prescription. The primary end point was the incidence rate of respiratory-related ED visits, compared using a reduced zero-inflated Poisson regression model. We also compared severe exacerbation rates and rescue medication use. Results A total of 93,980 patients were studied, including 67,251 (72%) in the dose counter cohort and 26,729 (28%) in the non-dose-counter cohort. The cohorts were broadly similar at baseline (55,069 [59%] female patients; median age, 37 years). The incidence rate of respiratory-related ED visits during the outcome year was 45% lower in the dose counter cohort than in the non-dose-counter cohort (adjusted rate ratio: 0.55; 95% confidence interval: 0.47–0.64). Exacerbation rates and short-acting β-agonist use were similar between cohorts. Conclusion These findings suggest that dose counter integration into albuterol MDIs is associated with decreased ED visit rates. The presence of integrated dose counters on rescue inhalers can help patients avoid using an empty or near-empty inhaler during exacerbations, thereby ensuring available medication for relief of their symptoms. Integrated dose counters on rescue MDIs could represent a simple and effective tool to improve clinical outcomes

  16. HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

    SciTech Connect

    Strenge, D.L.; Peloquin, R.A.

    1981-04-01

    The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure mode are also printed if requested.

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

    PubMed Central

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

    2010-01-01

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

  18. Inhalants

    MedlinePlus

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

  19. Efficacy of salbutamol by nebulizer versus metered dose inhaler with home-made non-valved spacer in acute exacerbation of childhood asthma.

    PubMed

    Yasmin, S; Mollah, A H; Basak, R; Islam, K T; Chowdhury, Y S

    2012-01-01

    This study was done to evaluate and to compare the efficacy of jet nebulizer and metered dose inhaler (MDI) with home-made non-valved spacer (HM NVS) to deliver aerosolized salbutamol in acute exacerbation of asthma in children. HM NVS was made by 500ml plastic mineral water bottle. It was perforated at the bottom for the insertion of MDI and proximal end was cut for placing the mouth. This prospective randomized study was conducted in the department of Pediatrics, Dhaka Medical College Hospital, during April 2007 to March 2008 with 50 known cases (2-12 years) of bronchial asthma with acute exacerbation. After randomized enrollment, each patient received three doses of salbutamol either through a jet nebulizer or through a HM NVS. Oxygen saturation (SaO2), wheeze, heart rate, respiratory rate were recorded throughout the treatment period. Data were analyzed with SPSS for Windows 10.0 at p value <0.05 was considered significant. The mean age of patients was 59.8 months in nebulizer group versus 69.4 months in MDI with HM NVS group. Baseline clinical characteristics in nebulizer group were SaO2 87.7±2.5 versus 89.0±1.8 percent, RR 59.2±7.3 vs. 63.2±4.8 per minute, HR 155.4±11.8 versus 149.0±10.8 per minute and wheeze in 22(88.0%) cases versus 21(84.0%) cases respectively (p>0.05). After therapy improvement was noted among the nebulizer group (SaO2 87.7±2.5 vs. 94.3±2.8 percent; RR 59.2±7.3 vs. 39.3±4.9 per minute; HR 155.4±11.8 vs. 151.60±17.3 per minute; wheeze 88% vs. 8%) as well as in the MDI with HM NVS group (SaO2 89.0±1.8 vs. 94.8±1.8 percent; RR 63.2±4.8 vs. 38.7±6.4 per minute; HR 149.0±10.8 vs. 144.5±13.5 per minute; wheeze 84% vs. 16%) [p<0.001; CI:95%]. However, these improvements did not differ significantly between the nebulizer group and HM NVS group (SaO2 94.3±2.8 vs. 94.8±1.8 percent, RR 39.3±4.9 vs. 38.7±6.4 per minute, HR 151.60±17.3 vs. 144.5±13.5 per minute and wheeze persisted in 2(8.0%) cases versus 4(16.0%) cases

  20. Radiation dose to the respiratory airway linings from inhalation of (/sup 15/O)-carbon dioxide

    SciTech Connect

    Bigler, R.E.; Sgouros, G.; Zanzonico, P.B.; Cosma, M.; Leonard, R.W.; Dahl, J.R.

    1985-05-01

    Estimates of the radiation dose to the upper airways including the trachea, oropharnyx, and nasal linings from inhalation of oxygen-15 labeled CO/sub 2/ studies are provided. Three air administration procedures were examined; inhalation by nose, by mouth and by mouth through a mouthpiece. Attention is given to the inhaled radioactive gas absorbed and retained in the mucus and saliva layers lining the respiratory passages. The authors estimates from direct measurements in saliva and mucus of the highest total radiation dose is to the oropharnyx (5.2 rads, mouth; 2.8 rads, nose). The dose to the trachea was estimated to be 3.5 rads from mucus measurements from dogs. The comparative dose to lungs is 1.2 rads (Bigler and Sgouros, JNM 24:431, 1983). These doses are for steady-state measurements involving the breathing of 1 mCi/1-air for 1 hr. Single breath estimates can be obtained by dividing by the number of breaths per hr (720). Although this procedure leads to a 10% reduction in the radiation dose to the lung, the radiation dose to the lining of the vein infused is high, ranging from 70 to 430 rads for equal activity administered. The authors recommend considering the lung as the tissue at highest risk for both inhalation and IV administration procedures.

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

    PubMed Central

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

    1994-01-01

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

  2. Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

    PubMed

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

    2016-04-01

    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. PMID:26880225

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

    PubMed Central

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

    2013-01-01

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

  4. Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit.

    PubMed

    Gutting, Bradford W; Marchette, David; Sherwood, Robert; Andrews, George A; Director-Myska, Alison; Channel, Stephen R; Wolfe, Daniel; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Rukhin, Andrey

    2013-07-21

    There is a need to advance our ability to conduct credible human risk assessments for inhalational anthrax associated with exposure to a low number of bacteria. Combining animal data with computational models of disease will be central in the low-dose and cross-species extrapolations required in achieving this goal. The objective of the current work was to apply and advance the competing risks (CR) computational model of inhalational anthrax where data was collected from NZW rabbits exposed to aerosols of Ames strain Bacillus anthracis. An initial aim was to parameterize the CR model using high-dose rabbit data and then conduct a low-dose extrapolation. The CR low-dose attack rate was then compared against known low-dose rabbit data as well as the low-dose curve obtained when the entire rabbit dose-response data set was fitted to an exponential dose-response (EDR) model. The CR model predictions demonstrated excellent agreement with actual low-dose rabbit data. We next used a modified CR model (MCR) to examine disease incubation period (the time to reach a fever >40 °C). The MCR model predicted a germination period of 14.5h following exposure to a low spore dose, which was confirmed by monitoring spore germination in the rabbit lung using PCR, and predicted a low-dose disease incubation period in the rabbit between 14.7 and 16.8 days. Overall, the CR and MCR model appeared to describe rabbit inhalational anthrax well. These results are discussed in the context of conducting laboratory studies in other relevant animal models, combining the CR/MCR model with other computation models of inhalational anthrax, and using the resulting information towards extrapolating a low-dose response prediction for man. PMID:23567649

  5. Inhalational drug delivery from seven different spacer devices.

    PubMed Central

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

    1996-01-01

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

  6. MICRO DOSE ASESSMENT OF INHALED PARTICLES IN HUMAN LUNGS: A STEP CLOSER TOWARDS THE TARGET TISSUE DOSE

    EPA Science Inventory

    Rationale: Inhaled particles deposit inhomogeneously in the lung and this may result in excessive deposition dose at local regions of the lung, particularly at the anatomic sites of bifurcations and junctions of the airways, which in turn leads to injuries to the tissues and adve...

  7. Inhalation and external doses in coastal villages of high background radiation area in Kollam, India.

    PubMed

    Ben Byju, S; Koya, P K M; Sahoo, B K; Jojo, P J; Chougaonkar, M P; Mayya, Y S

    2012-11-01

    The observational evidence for radiation-induced health effects in humans comes largely from the exposures to high doses received over short periods of time. The rate of induction of any health risk at low doses and dose rates is estimated by extrapolation from observations at high doses. Effects of low dose/low dose rate could be done by the study of populations that have been exposed to slightly above-average natural radiation doses. Southwest coastal line of the Kerala state in India is one such region known to have elevated levels of background radioactivity mainly due to the mineral-rich sand available with high abundance of thorium. In the present work, a study was conducted to investigate the inhalation and external radiation doses to human beings in the high background radiation area along the southwest coast of Kerala. Five hundred dwellings were selected for the study. All the selected houses were at least 10 y old with similar construction. Long-term integrated indoor measurements of the external gamma dose using thermoluminescent dosemeters (TLDs) and the inhalation dose with the SSNTD-based twin-cup dosemeters were carried out in the dwellings simultaneously. Ambient gamma dose measurements were also made with a GM tube-based survey meter while deploying and retrieving the dosemeters. The data show a high degree of heterogeneity. The inhalation dose was found to vary from 0.1 to 3.53 mSv y(-1) and the external dose rates had a range of 383-11419 µGy y(-1). The external doses measured by the survey meter and TLDs showed an excellent correlation. PMID:22961502

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

    PubMed Central

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

    2012-01-01

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

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

    EPA Science Inventory

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

  10. Calculates External and Inhalation Doses from Acute Radionuclide Releases on the Hanford Site.

    Energy Science and Technology Software Center (ESTSC)

    1984-03-02

    HADOC (Hanford Acute Dose Calculations) calculates external and inhalation doses resulting from postulated accidental radionuclide releases on the Hanford site. It generates doses to an individual at a specified location and to the population in the region near the Hanford site for specified organs. Doses reported include the maximally exposed individual's dose (by organ and exposure mode) and the total population dose (by organ and exposure mode) in the sector having the highest population exposuremore » factor. The first year and fifty-year dose commitments are reported. Optional reports giving the fractional contribution to total dose by radionuclide for each organ and dose commitment period for a maximally exposed individual and the population may be printed.« less

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    1992-04-01

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

  13. Metabolite profiles of rats in repeated dose toxicological studies after oral and inhalative exposure.

    PubMed

    Fabian, E; Bordag, N; Herold, M; Kamp, H; Krennrich, G; Looser, R; Ma-Hock, L; Mellert, W; Montoya, G; Peter, E; Prokudin, A; Spitzer, M; Strauss, V; Walk, T; Zbranek, R; van Ravenzwaay, B

    2016-07-25

    The MetaMap(®)-Tox database contains plasma-metabolome and toxicity data of rats obtained from oral administration of 550 reference compounds following a standardized adapted OECD 407 protocol. Here, metabolic profiles for aniline (A), chloroform (CL), ethylbenzene (EB), 2-methoxyethanol (ME), N,N-dimethylformamide (DMF) and tetrahydrofurane (THF), dosed inhalatively for six hours/day, five days a week for 4 weeks were compared to oral dosing performed daily for 4 weeks. To investigate if the oral and inhalative metabolome would be comparable statistical analyses were performed. Best correlations for metabolome changes via both routes of exposure were observed for toxicants that induced profound metabolome changes. e.g. CL and ME. Liver and testes were correctly identified as target organs. In contrast, route of exposure dependent differences in metabolic profiles were noted for low profile strength e.g. female rats dosed inhalatively with A or THF. Taken together, the current investigations demonstrate that plasma metabolome changes are generally comparable for systemic effects after oral and inhalation exposure. Differences may result from kinetics and first pass effects. For compounds inducing only weak changes, the differences between both routes of exposure are visible in the metabolome. PMID:27153797

  14. Quantitative assessment of inhalation exposure and deposited dose of aerosol from nanotechnology-based consumer sprays†

    PubMed Central

    Nazarenko, Yevgen; Lioy, Paul J.; Mainelis, Gediminas

    2015-01-01

    This study provides a quantitative assessment of inhalation exposure and deposited aerosol dose in the 14 nm to 20 μm particle size range based on the aerosol measurements conducted during realistic usage simulation of five nanotechnology-based and five regular spray products matching the nano-products by purpose of application. The products were also examined using transmission electron microscopy. In seven out of ten sprays, the highest inhalation exposure was observed for the coarse (2.5–10 μm) particles while being minimal or below the detection limit for the remaining three sprays. Nanosized aerosol particles (14–100 nm) were released, which resulted in low but measurable inhalation exposures from all of the investigated consumer sprays. Eight out of ten products produced high total deposited aerosol doses on the order of 101–103 ng kg−1 bw per application, ~85–88% of which were in the head airways, only <10% in the alveolar region and <8% in the tracheobronchial region. One nano and one regular spray produced substantially lower total deposited doses (by 2–4 orders of magnitude less), only ~52–64% of which were in the head while ~29–40% in the alveolar region. The electron microscopy data showed nanosized objects in some products not labeled as nanotechnology-based and conversely did not find nano-objects in some nano-sprays. We found no correlation between nano-object presence and abundance as per the electron microscopy data and the determined inhalation exposures and deposited doses. The findings of this study and the reported quantitative exposure data will be valuable for the manufacturers of nanotechnology-based consumer sprays to minimize inhalation exposure from their products, as well as for the regulators focusing on protecting the public health. PMID:25621175

  15. Dioxin inhalation doses from wood combustion in indoor cookfires

    NASA Astrophysics Data System (ADS)

    Northcross, Amanda L.; Katharine Hammond, S.; Canuz, Eduardo; Smith, Kirk R.

    2012-03-01

    Approximately 3 billion people worldwide rely on solid biomass fuels for household cooking and space heating, and approximately 50-60% use wood, often indoors in poorly ventilated situations. Daily exposures to high concentrations of smoke from cookstoves inside kitchens create large smoke exposures for women cooks and their small children. The smoke from burning the wood fuel contains hundred of toxic compounds, including dioxins and furans some of the most toxic compounds known to science. Health effects from exposure to dioxins include reproductive and developmental problems, damage the immune system, interference with hormones and also cause cancer. This study measured concentrations of dioxins and furans in a typical Guatemalan village home during open cookfires. Measured concentrations averaged 0.32 ± 0.07 ng m-3 over 31 fires. A Monte Carlo simulation was conducted using parameter estimates based on 8 years of research experience in the study area. The estimated total daily intake of 17 particle phase dioxin and furans for women, a 5-year-old child and a 6-month-old infant were 1.2 (S.D. = 0.4), 1.7 (S.D. = 0.7) and 2.0 (S.D. = 0.5) respectively. The 46% of babies have and estimated total daily intake (TDI) which exceed the WHO TDI guideline for dioxins and furans, 3% of women and 26% of 5-year-old children based solely inhalation of particle phase dioxins in woodsmoke from an open cooking fire. These values maybe underestimates, as they did not include gas phase concentrations or ingestion of dioxins and furans through food, which is the largest route of exposure in the developed world.

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

    PubMed Central

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

    2015-01-01

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

  17. Respiratory dose assessment of inhaled particles: continuing progress

    EPA Science Inventory

    Internal dose is a key factor for determining the health risk ofinhaled pollutant particles on the one hand and the efficacy ofdrug inhalantsonthe other. Accurateestimation ofrespiratorydose, however, is a difficult task because multiple factors come to play roles in the process....

  18. Immune sensitization to methylene diphenyl diisocyanate (MDI) resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

    PubMed Central

    2011-01-01

    Background Methylene diphenyl diisocyanate (MDI), a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v) of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA), while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL). Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary) respiratory tract inflammation and eosinophilia depended upon the (primary) skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI). The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma pathogenesis. MDI

  19. Adrenal insufficiency in a woman secondary to standard-dose inhaled fluticasone propionate therapy

    PubMed Central

    Hay, Casey M; Spratt, Daniel I

    2014-01-01

    Summary A 55-year-old woman with asthma presented with adrenal insufficiency of unknown origin. She was referred to our Division of Reproductive Endocrinology to further evaluate an undetectable morning cortisol level discovered during the evaluation of a low serum DHEA-S level. She was asymptomatic other than having mild fatigue and weight gain. Her medication list included 220 μg of inhaled fluticasone propionate twice daily for asthma, which she was taking as prescribed. On presentation, the undetectable morning cortisol level was confirmed. A urinary measurement of fluticasone propionate 17β-carboxylic acid was markedly elevated. Fluticasone therapy was discontinued and salmeterol therapy initiated with supplemental hydrocortisone. Hydrocortisone therapy was discontinued after 2 months. A repeat urinary fluticasone measurement 4 months after the discontinuation of fluticasone therapy was undetectably low and morning cortisol level was normal at 18.0 μg/dl. Inhaled fluticasone is generally considered to be minimally systemically absorbed. This patient's only clinical evidence suggesting adrenal insufficiency was fatigue accompanying a low serum DHEA-S level. This case demonstrates that adrenal insufficiency can be caused by a routine dose of inhaled fluticasone. Missing this diagnosis could potentially result in adrenal crisis upon discontinuation of fluticasone therapy. Learning points Standard-dose inhaled fluticasone can cause adrenal insufficiency.Adrenal insufficiency should be considered in patients taking, or who have recently discontinued, inhaled fluticasone therapy and present with new onset of nonspecific symptoms such as fatigue, weakness, depression, myalgia, arthralgia, unexplained weight loss, and nausea that are suggestive of adrenal insufficiency.Adrenal insufficiency should be considered in postoperative patients who exhibit signs of hypoadrenalism after fluticasone therapy has been withheld in the perioperative setting.Routine screening

  20. Bronchodilatory therapy with nebuhaler: how important is the delay between firing the dose and inhaling?

    PubMed

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

    1988-07-01

    Metered dose inhalers are sometimes used in conjunction with NebuhalerR, a 750 ml holding chamber, but the permissible delay time between actuating the aerosol into Nebuhaler and commencing inhalation is unknown. We have compared in 10 asthmatic patients the bronchodilator responses following inhalations of terbutaline sulphate from Nebuhaler after delays of 1, 5 and 30 seconds and following placebo inhalation. Terbutaline sulphate was administered as 2 puffs, each of 250 micrograms, separated by approximately 15 minutes. After each delay time, terbutaline produced increases in forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR) and maximum expiratory flow following exhalation of 75% of the forced vital capacity (V max25) significantly greater than those after placebo (P less than 0.01). Changes in PEFR did not vary significantly among the three delay times, but the increases in FEV1 and in V max25 were significantly reduced with 30 seconds' delay. It is concluded that the delay between actuation into Nebuhaler and commencing inhalation can be extended from 1 second to 5 seconds without significant loss of drug efficacy, and that further extension to 30 seconds causes only a small loss of bronchodilatation: hence the delay time is unlikely to be of major importance in clinical practice. PMID:3073806

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

    PubMed

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

    2009-01-01

    N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister. PMID:20088245

  2. Inhalation of racemic epinephrine in children with asthma. Dose-response relation and comparison with salbutamol.

    PubMed

    Kjellman, B; Tollig, H; Wettrell, G

    1980-10-01

    In this study the effects of nebulized racemic epinephrine (Micronephrine) were investigated in children with asthma. The drug was inhaled by a compressor nebulizer with a plastic mask. In the first part of the study it is shown that nebulized Micronephrine has a dose-dependent bronchodilatory effect. In the second part the effect is compared with that of nebulized salbutamol in 10 children (7-16 years of age) with bronchial asthma. The highest dose used in the dose-response trials (=0.9 mg Micronephrine/kg body-weight) was compared with 0.15 mg salbutamol/kg body-weight, which is the dose commonly used in Sweden. There was no significant difference between the drugs as regards increase of forced expiratory volume in 1 sec or duration of the increase. There was a small but significant increase in systolic blood pressure, measured 5 min after the inhalation of Micronephrine but no significant change in diastolic pressure or heart rate. Four children complained of temporary sore throat after the inhalation. PMID:7468946

  3. Quantitative dose-response assessment of inhalation exposures to toxic air pollutants

    SciTech Connect

    Jarabek, A.M.; Foureman, G.L.; Gift, J.S.; Guth, D.J.

    1997-12-31

    Implementation of the 1990 Clean Air Act Amendments, including evaluation of residual risks. requires accurate human health risk estimates of both acute and chronic inhalation exposures to toxic air pollutants. The U.S. Environmental Protection Agency`s National Center for Environmental Assessment, Research Triangle Park, NC, has a research program that addresses several key issues for development of improved quantitative approaches for dose-response assessment. This paper describes three projects underway in the program. Project A describes a Bayesian approach that was developed to base dose-response estimates on combined data sets and that expresses these estimates as probability density functions. A categorical regression model has been developed that allows for the combination of all available acute data, with toxicity expressed as severity categories (e.g., mild, moderate, severe), and with both duration and concentration as governing factors. Project C encompasses two refinements to uncertainty factors (UFs) often applied to extrapolate dose-response estimates from laboratory animal data to human equivalent concentrations. Traditional UFs have been based on analyses of oral administration and may not be appropriate for extrapolation of inhalation exposures. Refinement of the UF applied to account for the use of subchronic rather than chronic data was based on an analysis of data from inhalation exposures (Project C-1). Mathematical modeling using the BMD approach was used to calculate the dose-response estimates for comparison between the subchronic and chronic data so that the estimates were not subject to dose-spacing or sample size variability. The second UF that was refined for extrapolation of inhalation data was the adjustment for the use of a LOAEL rather than a NOAEL (Project C-2).

  4. Uncertainties in electron-absorbed fractions and lung doses from inhaled beta-emitters.

    PubMed

    Farfán, Eduardo B; Bolch, Wesley E; Huston, Thomas E; Rajon, Didier A; Huh, Chulhaeng; Bolch, W Emmett

    2005-01-01

    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. PMID:15596988

  5. Ability to learn inhaler technique in relation to cognitive scores and tests of praxis in old age

    PubMed Central

    Allen, S; Ragab, S

    2002-01-01

    Clinical observations have shown that some older patients are unable to learn to use a metered dose inhaler (MDI) despite having a normal abbreviated mental test (AMT) score, possibly because of dyspraxia or unrecognised cognitive impairment. Thirty inhaler-naive inpatients (age 76–94) with an AMT score of 8–10 (normal) were studied. Standard MDI training was given and the level of competence reached was scored (inhalation score). A separate observer performed the minimental test (MMT), Barthel index, geriatric depression score (GDS), ideational dyspraxia test (IDT), and ideomotor dyspraxia test (IMD). No correlative or threshold relationship was found between inhalation score and Barthel index, GDS, or IDT. However, a significant correlation was found between inhalation score and IMD (r = 0.45, p = 0.039) and MMT (r = 0.48, p = 0.032) and threshold effects emerged in that no subject with a MMT score of less than 23/30 had an inhalation score of 5/10 or more (adequate technique requires 6/10 or more), and all 17/18 with an inhalation score of 6/10 or more had an IMD of 14/20 or more. The three patients with a MMT >22 and inhalation score <6 had abnormal IMD scores. Inability to learn an adequate inhaler technique in subjects with a normal AMT score appears to be due to unrecognised cognitive impairment or dyspraxia. The MMT is probably a more useful screening test than the AMT score in this context. PMID:11796871

  6. Inhaled nitric oxide: Dose response and the effects of blood in the isolated rat lung

    SciTech Connect

    Rich, G.F.; Roos, C.M.; Anderson, S.M.; Urich, D.C.; Daugherty, M.O.; Johns, R.A. )

    1993-09-01

    Inhaled nitric oxide (NO) is a vasodilator selective to the pulmonary circulation. Using isolated rat lungs, the authors determined the dose-response relationship of NO and the role of blood in mediating pulmonary vasodilation and selectivity. Inhaled 20, 50, 100, and 1,000 ppm NO attenuated (P < 0.001) hypoxic pulmonary vasoconstriction by 16.1 [+-] 4.9, 22.6 [+-] 6.8, 28.4 [+-] 3.5, and 69.3 [+-] 4.2%, respectively. Inhaled 13, 34, 67, and 670 ppm NO attenuated the increase in pulmonary arterial pressure secondary to angiotensin II more (P < 0.001) in Greenberg-Bohr buffer- (GB) than in blood-perfused lungs (51.7 [+-] 0.0, 71.9 [+-] 8.9, 78.2 [+-] 5.3, and 91.9 [+-] 2.1% vs. 14.3 [+-] 4.2, 23.8 [+-] 4.6, 28.4 [+-] 3.8, and 55.5 [+-] 5.9%, respectively). Samples from GB- but not blood-perfused lungs contained NO (93.0 [+-] 26.3 nM). Intravascular NO attenuated the response to angiotensin II more (P < 0.001) in GB- (with and without plasma) than in blood- (hematocrit = 41 and 5%) perfused lungs (75.6 [+-] 6.4 and 70.9 [+-] 4.8% vs. 22.2 [+-] 2.4 and 39.4 [+-] 7.6%). In conclusion, inhaled NO produces reversible dose-dependent pulmonary vasodilation over a large range of concentrations. Inhaled NO enters the circulation, but red blood cells prevent systematic vasodilation and also a significant amount of pulmonary vasodilation. 24 refs., 7 figs., 2 tabs.

  7. High- and low-dose allergen challenges in asthmatic patients using inhaled corticosteroids

    PubMed Central

    Lee, Wha-Yong; Southworth, Thomas; Booth, Steven; Singh, Dave

    2015-01-01

    Aims The inhaled allergen challenge model has been used previously to investigate the effects of novel anti-inflammatory drugs in inhaled corticosteroid (ICS)-naïve asthmatics. The aim of this study was to characterize high- and low-dose allergen challenges in asthmatic patients using ICS. Methods Twenty-eight asthmatic patients taking ICS (beclomethasone equivalent <1000 μg day−1) were recruited for high-dose allergen challenge, of whom 10 subsequently also had a repeat low-dose challenge comprising seven allergen challenges. Induced sputum was collected for measurements of cell counts and supernatant biomarkers. Results The high-dose allergen challenge caused an early and late asthmatic response in 19 of 28 patients; the mean maximal fall in the forced expiratory volume in 1 s (FEV1) was 29.1% (SD 6.2%) and 25.1% (SD 9.6%), respectively. There was also an increase in sputum eosinophils of 6.2% (P = 0.0004), as well as supernatant eosinophil cationic protein levels. The low-dose allergen challenge caused an acute fall in FEV1, but had no effect on FEV1 at 24 h after challenge or sputum measurements. Conclusions The high-dose allergen challenge in asthmatics using ICS induces a late asthmatic response associated with an increase in eosinophilic airway inflammation. This may be a suitable model for studying the effects of novel anti-inflammatory drugs added to maintenance ICS treatment. PMID:25214200

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

    SciTech Connect

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

    1986-04-01

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

  9. Exposure versus internal dose: Respiratory tract deposition modeling of inhaled asbestos fibers in rats and humans (Presentation Poster)

    EPA Science Inventory

    Exposure to asbestos is associated with respiratory diseases, including asbestosis, lung cancer and mesothelioma. Internal fiber dose depends on fiber inhalability and orientation, fiber density, length and width, and various deposition mechanisms (DM). Species-specific param...

  10. Influence of flow rate on aerosol particle size distributions from pressurized and breath-actuated inhalers.

    PubMed

    Smith, K J; Chan, H K; Brown, K F

    1998-01-01

    Particle size distribution of delivered aerosols and the total mass of drug delivered from the inhaler are important determinants of pulmonary deposition and response to inhalation therapy. Inhalation flow rate may vary between patients and from dose to dose. The Andersen Sampler (AS) cascade impactor operated at flow rates of 30 and 55 L/min and the Marple-Miller Impactor (MMI) operated at flow rates of 30, 55, and 80 L/min were used in this study to investigate the influence of airflow rate on the particle size distributions of inhalation products. Total mass of drug delivered from the inhaler, fine particle mass, fine particle fraction, percentage of nonrespirable particles, and amount of formulation retained within the inhaler were determined by ultraviolet spectrophotometry for several commercial bronchodilator products purchased in the marketplace, including a pressurized metered-dose inhaler (pMDI), breath-actuated pressurized inhaler (BAMDI), and three dry powder inhalers (DPIs), two containing salbutamol sulphate and the other containing terbutaline sulphate. Varying the flow rate through the cascade impactor produced no significant change in performance of the pressurized inhalers. Increasing the flow rate produced a greater mass of drug delivered and an increase in respirable particle mass and fraction from all DPIs tested. PMID:10346666

  11. The ELLIPTA® Dry Powder Inhaler: Design, Functionality, In Vitro Dosing Performance and Critical Task Compliance by Patients and Caregivers.

    PubMed

    Grant, Andrew C; Walker, Richard; Hamilton, Melanie; Garrill, Karl

    2015-12-01

    Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy. The ELLIPTA(®) DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease. It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication. Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration. There are three principal operating steps to administer a dose: open, inhale, close. This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler. Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (≥30 L/min) and over its 30-day in-use life. Data from the human factors validation tests demonstrated that almost all participants (≥97%) were able to complete each of the steps required to prepare a dose for inhalation without error. Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options. It also improves patient ease-of-use when compared with the DISKUS(®) DPI. PMID:26372466

  12. The ELLIPTA® Dry Powder Inhaler: Design, Functionality, In Vitro Dosing Performance and Critical Task Compliance by Patients and Caregivers

    PubMed Central

    Grant, Andrew C.; Hamilton, Melanie; Garrill, Karl

    2015-01-01

    Abstract Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy. The ELLIPTA® DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease. It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication. Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration. There are three principal operating steps to administer a dose: open, inhale, close. This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler. Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (≥30 L/min) and over its 30-day in-use life. Data from the human factors validation tests demonstrated that almost all participants (≥97%) were able to complete each of the steps required to prepare a dose for inhalation without error. Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options. It also improves patient ease-of-use when compared with the DISKUS® DPI. PMID:26372466

  13. Addition of Montelukast to Low-Dose Inhaled Corticosteroid Leads to Fewer Exacerbations in Older Patients Than Medium-Dose Inhaled Corticosteroid Monotherapy

    PubMed Central

    Ye, Young-Min; Kim, Sang-Ha; Hur, Gyu-Young; Kim, Joo-Hee; Park, Jung-Won; Shim, Jae Jeong; Jung, Ki-Suck; Lee, Hyun-Young

    2015-01-01

    Purpose There have been few reports regarding the efficacy of antiasthmatics in older patients. To compare the efficacy of the addition of montelukast to low-dose inhaled budesonide (MON-400BUD) versus increasing the dose of inhaled steroid (800BUD) on asthma control in older asthmatics. Methods A randomized, open-label, parallel-designed trial was conducted for 12 weeks. The primary endpoint was the rate of patients who reached "well-controlled asthma status" after the 12-week treatment period. Additionally, asthma exacerbations, sputum inflammatory cells, asthma control test (ACT) and physical functioning scale (PFS), and adverse reactions were monitored. Results Twenty-four (36.9%) and 22 (34.9%) subjects in the MON-400BUD (n=65) and 800BUD (n=63) groups had well-controlled asthma at the end of the study, respectively. The numbers of asthma exacerbations requiring oral corticosteroid treatment (20 vs 9, respectively, P=0.036) and the development of sore throat (22 vs 11, respectively, P=0.045) were significantly higher in the 800BUD group than in the MON-400BUD group. Body mass index and changes in ACT, FEV1%, 6-min walk distance and PFS from baseline were all significant determinants for distinguishing subjects with well-controlled and partly controlled asthma from those with uncontrolled asthma (P<0.05) at the end of the study. Conclusions The efficacy of 12-week treatment with MON-400BUD in older asthmatics was comparable to that of 800BUD on asthma control but associated with reduced frequency of asthma exacerbations requiring oral steroids and sore throat events. Changes in ACT and PFS can be useful predictors of asthma control status in older patients. PMID:26122504

  14. Delivery of formoterol from a novel multi-dose inhaler Airmax.

    PubMed

    Zeng, X M; Jones, S; O'Leary, D; Phelan, M; Colledge, J

    2002-06-01

    Using a proprietary technology known as the X-ACT system--Active-metering, Cyclone-separator Technology, a novel multi-dose inhaler (Airmax) was developed to provide accurate and consistent dosing and a high-fine particle fraction ofthe drug. Formoterol, present as a blend with lactose monohydrate was delivered from Airmax to obtain a nominal formoterol dose of 6 or 12 microg. The devices were tested using a five-stage liquid impinger and a unit dose sampling apparatus, operated under conditions specified in European Pharmacopoeia (2000). Fine-particle dose (FPD) was defined as the dose of the aerosolized drug particles with an aerodynamic diameter < 5 microm and fine particle fraction (FPF) was the ratio of FPD to the total recovered dose. Dose per actuation was found to be 97.0+/-11.5% label claim (LC) or 5.8+/-0.7 microg (n = 140), and 100+/-9.4% LC or 12+/-1.1 microg (n=440), for the 6 and 12 microg strengths, respectively. The mass median aerodynamic diameter was 2.4+/-0.1 microm (n = 14), the geometric standard deviation 2.1+/-0.1 (n = 14), and FPF 44.4+/-24% (n= 14) for both strengths. Thus, the combination of active metering and cyclone separator produces highly consistent doses of formoterol that have a large respirable fraction. PMID:12117038

  15. [A new spacer, Babyhaler, for BDP inhalation therapy in severe infantile asthma].

    PubMed

    Yamada, Y; Yoshihara, S; Abe, T; Fukuda, N; Watanabe, M; Ono, M; Arisaka, O

    2000-11-01

    Recently, it has been recognized that airway inflammation is the most important pathogenesis of bronchial asthma, and inhaled corticosteroids therapy is effective for childhood asthma. However, using metered dose inhalers (MDI) of beclomethasone dipropionate (BDP) is difficult for infants. In this study, we administered BDP inhalation therapy with a new spacer, Babyhaler, for five cases of early childhood with severe infantile asthma that we could not control even by combination of theophylline round the clock (RTC) therapy and disodium cromoglycate (DSCG) + beta 2 stimulant (beta 2) regular use. We compared symptom score of asthma attack between the pre-treatment period (prior 2 weeks) and post-treatment period (following 8 weeks) of BDP inhalation therapy with Babyhaler. As a result, symptom score decreased significantly within 4 weeks after treatment of BDP with Babyhaler as compared with the score before treatment of BDP. These findings suggest that Babyhaler is useful for BDP inhalation therapy in infantile asthma. PMID:11193463

  16. Inhaled beclometasone dipropionate/formoterol fumarate extrafine fixed combination for the treatment of asthma.

    PubMed

    Crisafulli, Ernesto; Zanini, Andrea; Pisi, Giovanna; Pignatti, Patrizia; Poli, Gianluigi; Scuri, Mario; Chetta, Alfredo

    2016-05-01

    Inhaled therapy is often considered the cornerstone of asthma management and international guidelines recommend combination therapy of inhaled corticosteroids (ICS) and long-acting-beta2-agonists (LABA) in a large proportion of asthmatic patients. The effectiveness of ICS/LABA is dependent on the correct choice of device and proper inhalation technique, this influences drug delivery and distribution along the bronchial tree, including the most peripheral airways. The fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/FF) is the only extrafine formulation available in pressurized metered dose inhaler (pMDI) and in dry powder inhaler (DPI). Here, we focus on the recent significant advances regarding BDP/FF fixed combination for the treatment of asthma. PMID:26938578

  17. In silico modeling of spore inhalation reveals fungal persistence following low dose exposure

    PubMed Central

    Tanaka, Reiko J.; Boon, Neville J.; Vrcelj, Katarina; Nguyen, Anita; Vinci, Carmelina; Armstrong-James, Darius; Bignell, Elaine

    2015-01-01

    The human lung is constantly exposed to spores of the environmental mould Aspergillus fumigatus, a major opportunistic pathogen. The spectrum of resultant disease is the outcome of complex host-pathogen interactions, an integrated, quantitative understanding of which lies beyond the ethical and technical reach permitted by animal studies. Here we construct a mathematical model of spore inhalation and clearance by concerted actions of macrophages and neutrophils, and use it to derive a mechanistic understanding of pathogen clearance by the healthy, immunocompetent host. In particular, we investigated the impact of inoculum size upon outcomes of single-dose fungal exposure by simulated titrations of inoculation dose, from 106 to 102 spores. Simulated low-dose (102) spore exposure, an everyday occurrence for humans, revealed a counter-intuitive prediction of fungal persistence (>3 days). The model predictions were reflected in the short-term dynamics of experimental murine exposure to fungal spores, thereby highlighting the potential of mathematical modelling for studying relevant behaviours in experimental models of fungal disease. Our model suggests that infectious outcomes can be highly dependent upon short-term dynamics of fungal exposure, which may govern occurrence of cyclic or persistent subclinical fungal colonisation of the lung following low dose spore inhalation in non-neutropenic hosts. PMID:26364644

  18. Tolerability in man following inhalation dosing of the selective TLR7 agonist, AZD8848

    PubMed Central

    Delaney, Stephen; Biffen, Mark; Maltby, Justine; Bell, John; Asimus, Sara; Aggarwal, Ajay; Kraan, Maarten; Keeling, David

    2016-01-01

    Background Many patients with asthma have a T-helper type 2 (Th2) driven inflammation of the lung, whereas toll-like receptor 7 (TLR7) agonists, by inducing type I interferons, inhibit Th2 responses. In man, oral or parenteral TLR7 agonists can induce influenza-like symptoms through systemic induction of type I interferons. Design of a TLR7 agonist that is only active in the lung could reduce the risk of side effects and offer a new means for treating asthma. We developed a TLR7 agonist antedrug, AZD8848, to determine its local and systemic effects in preclinical models and man. Methods In vitro cellular potencies for the TLR7 antedrug agonist, AZD8848, were determined along with pharmacokinetics and efficacy in a rat allergy model. Sputum and blood biomarkers were measured in single ascending and multiple ascending dose clinical studies following inhalation delivery of AZD8848 and tolerability assessed. Results AZD8848 was potent in cellular assays and pharmacokinetics confirmed lack of systemic exposure to AZD8848. Weekly lung dosing in an animal model showed efficacy 26 days beyond the final dose. In healthy volunteers, AZD8848 was initially well tolerated with target engagement being demonstrated by induction of CXCL10 in sputum. A second inhaled dose, given 1 week later, amplified the systemic interferon signal in more than half the participants and resulted in significant influenza-like symptoms. Conclusions The antedrug design restricted the direct actions of AZD8848 to the lung. However, the type I interferon induced locally by TLR7 spilled over systemically, limiting the utility of this inhaled antedrug approach. Trial registration number NCT01560234, NCT01818869. PMID:26933507

  19. [Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack].

    PubMed

    Solé, D; Rizzo, M C; Porto, I M; Gomez, I D; Sano, F; Figueiredo, M A; Naspitz, C K

    1996-01-01

    Patients during a mild to moderate acute attack of asthma (FEV1: 50 - 80% of predicted) were treated with Salmeterol MDI - 50mcg or Rotadisk - 50mcg or Salbutamol (MDI -200mcg). The children were followed by Spirometry, measuring FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every 60 minutes until 780 minutes, if the patients maintained the FEV1 above 80% of the predicted value and/or an increment of 20% in the VEF1 basal value. The Salmeterol group showed a significant bronchodilation at 60 minutes which was maintained in half of the patients up to 9 hours. This was not observed in the Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the bronchodilation effect was observed in half of the patients up to 6 hours. There were no significant differences between both presentations of Salmeterol. This drug allowed a prolonged bronchodilator effect and is, according to the several consensus on management of asthma, an adequate option in the treatment of moderate to severe asthma. PMID:14688969

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

    PubMed Central

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

    2015-01-01

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

  1. Age-specific inhalation radiation dose commitment factors for selected radionuclides

    SciTech Connect

    Strenge, D.L.; Peloquin, R.A.; Baker, D.A.

    1982-08-01

    Inhalation dose commitment factors are presented for selected radionuclides for exposure of individuals in four age groups: infant, child, teen and adult. Radionuclides considered are /sup 35/S, /sup 36/Cl, /sup 45/Ca, /sup 67/Ga, /sup 75/Se, /sup 85/Sr, /sup 109/Cd, /sup 113/Sn, /sup 125/I, /sup 133/Ba, /sup 170/Tm, /sup 169/Yb, /sup 182/Ta, /sup 192/Ir, /sup 198/Au, /sup 201/Tl, /sup 204/Tl, and /sup 236/Pu. The calculational method is based on the human metabolic model of ICRP as defined in Publication 2 (ICRP 1959) and as used in previous age-specific dose factor calculations by Hoenes and Soldat (1977). Dose commitment factors are presented for the following organs of reference: total body, bone, liver, kidney, thyroid, lung and lower large intestine.

  2. Modelling and mitigating dose to firefighters from inhalation of radionuclides in wildland fire smoke

    DOE PAGESBeta

    Viner, Brian J.; Jannik, Tim; Stone, Daniel; Hepworth, Allan; Naeher, Luke; Adetona, Olorunfemi; Blake, John; Eddy, Teresa

    2015-06-12

    Firefighters responding to wildland fires where surface litter and vegetation contain radiological contamination will receive a radiological dose by inhaling resuspended radioactive material in the smoke. This may increase their lifetime risk of contracting certain types of cancer. Using published data, we modelled hypothetical radionuclide emissions, dispersion and dose for 70th and 97th percentile environmental conditions and for average and high fuel loads at the Savannah River Site. We predicted downwind concentration and potential dose to firefighters for radionuclides of interest (137Cs, 238Pu, 90Sr and 210Po). Predicted concentrations exceeded dose guidelines in the base case scenario emissions of 1.0 ×more » 107 Bq ha–1 for 238Pu at 70th percentile environmental conditions and average fuel load levels for both 4- and 14-h shifts. Under 97th percentile environmental conditions and high fuel loads, dose guidelines were exceeded for several reported cases for 90Sr, 238Pu and 210Po. Potential for exceeding dose guidelines was mitigated by including plume rise (>2 m s–1) or moving a small distance from the fire owing to large concentration gradients near the edge of the fire. As a result, our approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.« less

  3. Modelling and mitigating dose to firefighters from inhalation of radionuclides in wildland fire smoke.

    SciTech Connect

    Viner, Brian J.

    2015-06-12

    Firefighters responding to wildland fires where surface litter and vegetation contain radiological contamination will receive a radiological dose by inhaling resuspended radioactive material in the smoke. This may increase their lifetime risk of contracting certain types of cancer. Using published data, we modelled hypothetical radionuclide emissions, dispersion and dose for 70th and 97th percentile environmental conditions and for average and high fuel loads at the Savannah River Site. We predicted downwind concentration and potential dose to firefighters for radionuclides of interest (137Cs, 238Pu, 90Sr and 210Po). Predicted concentrations exceeded dose guidelines in the base case scenario emissions of 1.0 x 107Bq ha-1 for 238Pu at 70th percentile environmental conditions and average fuel load levels for both 4- and 14-h shifts. Under 97th percentile environmental conditions and high fuel loads, dose guidelines were exceeded for several reported cases for 90Sr, 238Pu and 210Po. The potential for exceeding dose guidelines was mitigated by including plume rise (>2ms-1) or moving a small distance from the fire owing to large concentration gradients near the edge of the fire. This approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.

  4. Modelling and mitigating dose to firefighters from inhalation of radionuclides in wildland fire smoke

    SciTech Connect

    Viner, Brian J.; Jannik, Tim; Stone, Daniel; Hepworth, Allan; Naeher, Luke; Adetona, Olorunfemi; Blake, John; Eddy, Teresa

    2015-06-12

    Firefighters responding to wildland fires where surface litter and vegetation contain radiological contamination will receive a radiological dose by inhaling resuspended radioactive material in the smoke. This may increase their lifetime risk of contracting certain types of cancer. Using published data, we modelled hypothetical radionuclide emissions, dispersion and dose for 70th and 97th percentile environmental conditions and for average and high fuel loads at the Savannah River Site. We predicted downwind concentration and potential dose to firefighters for radionuclides of interest (137Cs, 238Pu, 90Sr and 210Po). Predicted concentrations exceeded dose guidelines in the base case scenario emissions of 1.0 × 107 Bq ha–1 for 238Pu at 70th percentile environmental conditions and average fuel load levels for both 4- and 14-h shifts. Under 97th percentile environmental conditions and high fuel loads, dose guidelines were exceeded for several reported cases for 90Sr, 238Pu and 210Po. Potential for exceeding dose guidelines was mitigated by including plume rise (>2 m s–1) or moving a small distance from the fire owing to large concentration gradients near the edge of the fire. As a result, our approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.

  5. Air classifier technology (ACT) in dry powder inhalation Part 3. Design and development of an air classifier family for the Novolizer multi-dose dry powder inhaler.

    PubMed

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

    2006-03-01

    In this study, the design of a multifarious classifier family for different applications is described. The main design and development steps are presented as well as some special techniques that have been applied to achieve preset objectives. It is shown by increasing the number of air supply channels to the classifier chamber (from 2 to 8), that the fine particle losses from adhesion onto the classifier walls can be reduced from 75% to less than 5% of the real dose for soft (spherical) agglomerates. By applying a bypass flow that is arranged as a co-axial sheath of clean air around the aerosol cloud from the classifier, the airflow resistance of the classifier can be controlled over a relatively wide range of values (0.023-0.041 kPa(0.5) min l(-1)). This, without affecting the fine particle dose or increasing the fine particle losses in the inhaler. Moreover, the sheath flow can be modelled to reduce the depositions in the induction port to the cascade impactor or in the patient's mouth, which are the result of back flows in these regions. The principle of powder induced pressure drop reduction across a classifier enables assessment of the amount of powder in the classifier at any moment during inhalation, from which classifier loading (from the dose system) and discharge rates can be derived. This principle has been applied to study the residence time of a dose in the classifier as function of the carrier size fraction and the flow rate. It has been found that this residence time can be controlled in order to obtain an optimal balance between the generated fine particle fraction and the inhalation manoeuvre of the patient. A residence time between 0.5 and 2 s at 60 l/min is considered favourable, as this yields a high fine particle dose (depending on the type of formulation used) and leaves sufficient inhaled volume for particle transport into the deep lung. PMID:16442248

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

    PubMed Central

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

    2015-01-01

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

  7. Estimates of internal-dose equivalent from inhalation and ingestion of selected radionuclides

    SciTech Connect

    Dunning, D.E.

    1982-01-01

    This report presents internal radiation dose conversion factors for radionuclides of interest in environmental assessments of nuclear fuel cycles. This volume provides an updated summary of estimates of committed dose equivalent for radionuclides considered in three previous Oak Ridge National Laboratory (ORNL) reports. Intakes by inhalation and ingestion are considered. The International Commission on Radiological Protection (ICRP) Task Group Lung Model has been used to simulate the deposition and retention of particulate matter in the respiratory tract. Results corresponding to activity median aerodynamic diameters (AMAD) of 0.3, 1.0, and 5.0 ..mu..m are given. The gastorintestinal (GI) tract has been represented by a four-segment catenary model with exponential transfer of radioactivity from one segment to the next. Retention of radionuclides in systemic organs is characterized by linear combinations of decaying exponential functions, recommended in ICRP Publication 30. The first-year annual dose rate, maximum annual dose rate, and fifty-year dose commitment per microcurie intake of each radionuclide is given for selected target organs and the effective dose equivalent. These estimates include contributions from specified source organs plus the systemic activity residing in the rest of the body; cross irradiation due to penetrating radiations has been incorporated into these estimates. 15 references.

  8. Ozone Inhalation Leads to a Dose-Dependent Increase of Cytogenetic Damage in Human Lymphocytes

    PubMed Central

    Holland, Nina; Davé, Veronica; Venkat, Subha; Wong, Hofer; Donde, Aneesh; Balmes, John R; Arjomandi, Mehrdad

    2014-01-01

    Ozone is an important constituent of ambient air pollution and represents a major public health concern. Oxidative injury due to ozone inhalation causes the generation of reactive oxygen species and can be genotoxic. To determine whether ozone exposure causes genetic damage in peripheral blood lymphocytes, we employed a well-validated cytokinesis-block micronucleus Cytome assay. Frequencies of micronuclei (MN) and nucleoplasmic bridges (NB) were used as indicators of cytogenetic damage. Samples were obtained from 22 non-smoking healthy subjects immediately before and 24-hr after controlled 4-hr exposures to filtered air, 100 ppb, and 200 ppb ozone while exercising in a repeated-measure study design. Inhalation of ozone at different exposure levels was associated with a significant dose-dependent increase in MN frequency (P < 0.0001) and in the number of cells with more than 1 MN per cell (P < 0.0005). Inhalation of ozone also caused an increase in the number of apoptotic cells (P = 0.002). Airway neutrophilia was associated with an increase in MN frequency (P = 0.033) independent of the direct effects of ozone exposure (P < 0.0001). We also observed significant increases in both MN and NB frequencies after exercise in filtered air, suggesting that physical activity is also an important inducer of oxidative stress. These results corroborate our previous findings that cytogenetic damage is associated with ozone exposure, and show that damage is dose-dependent. Further study of ozone-induced cytogenetic damage in airway epithelial cells could provide evidence for the role of oxidative injury in lung carcinogenesis, and help to address the potential public health implications of exposures to oxidant environments. PMID:25451016

  9. ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS

    EPA Science Inventory

    ANALYSIS OF RESPIRATORY DEPOSITION OF INHALED PARTICLES FOR DIFFERENT DOSE METRICS: COMPARISON OF NUMBER, SURFACE AREA AND MASS DOSE OF TYPICAL AMBIENT BI-MODAL AEROSOLS.
    Chong S. Kim, SC. Hu*, PA Jaques*, US EPA, National Health and Environmental Effects Research Laboratory, ...

  10. Inhalation reference dose (RfDi): an application of interspecies dosimetry modeling for risk assessment of insoluble particles.

    PubMed

    Jarabek, A M; Menache, M G; Overton, J H; Dourson, M L; Miller, F J

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses [the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity] for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated (Overton and Miller 1988). Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation. PMID:2606680

  11. Inhalation reference dose (RfDi): An application of interspecies dosimetry modeling for risk assessment of insoluble particles

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.; Dourson, M.L.; Miller, F.J. )

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated. Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

  12. Delivery characteristics and patients’ handling of two single-dose dry-powder inhalers used in COPD

    PubMed Central

    Chapman, Kenneth R; Fogarty, Charles M; Peckitt, Clare; Lassen, Cheryl; Jadayel, Dalal; Dederichs, Juergen; Dalvi, Mukul; Kramer, Benjamin

    2011-01-01

    For optimal efficacy, an inhaler should deliver doses consistently and be easy for patients to use with minimal instruction. The delivery characteristics, patients’ correct use, and preference of two single-dose dry powder inhalers (Breezhaler and HandiHaler) were evaluated in two complementary studies. The first study examined aerodynamic particle size distribution, using inhalation profiles of seven patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The second was an open-label, two-period, 7-day crossover study, evaluating use of the inhalers with placebo capsules by 82 patients with mild to severe COPD. Patients’ correct use of the inhalers was assessed after reading written instructions on Day 1, and after training and 7 days of daily use. Patients’ preference was assessed after completion of both study periods. Patient inhalation profiles showed average peak inspiratory flows of 72 L/minute through Breezhaler and 36 L/minute through HandiHaler. For Breezhaler and HandiHaler, fine particle fractions were 27% and 10%, respectively. In the second study, correct use of Breezhaler and HandiHaler was achieved by >77% of patients for any step after 7 days; 61% of patients showed an overall preference for Breezhaler and 31% for HandiHaler (P = 0.01). Breezhaler is a low-resistance inhaler suitable for use by patients with a range of disease severities. Most patients used both inhalers correctly after 7 days, but more patients showed an overall preference for the Breezhaler compared with the HandiHaler. These are important factors for optimum dose delivery and successful COPD management. PMID:21760722

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

    PubMed Central

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

    2012-01-01

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

  14. A dose-responsive model of smoke inhalation injury. Severity-related alteration in cardiopulmonary function.

    PubMed Central

    Shimazu, T; Yukioka, T; Hubbard, G B; Langlinais, P C; Mason, A D; Pruitt, B A

    1987-01-01

    The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by "unit"), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration. Images Fig. 3. Fig. 4A. Fig. 4B. PMID:3606236

  15. Can low-dose combination products for inhalation be formulated in single crystalline particles?

    PubMed

    Kumon, Michiko; Kwok, Philip Chi Lip; Adi, Handoko; Heng, Desmond; Chan, Hak-Kim

    2010-04-16

    This study aims to produce and test the performance of novel crystalline respirable particles containing two low-dose active ingredients and mannitol. This technique overcomes the usual requirement of blending with lactose carriers in formulating combination inhalation products. Ternary powders were produced by co-spray drying solutions containing an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA), and mannitol as a crystalline excipient. Two formulations comprising widely used ICS and LABA were studied: budesonide/formoterol fumarate dihydrate/mannitol (B/F/M-SD) and fluticasone propionate/salmeterol xinafoate/mannitol (F/S/M-SD). Various physicochemical properties of the powders were analyzed. Aerosol performance was evaluated by dispersing each powder from an Aerolizer at 60 and 100 L/min into a Next Generation Impactor. We obtained partially hollow spherical particles (volume median diameters of 2 microm) with drug-enriched surfaces. Both formulations contained alpha-mannitol, and the ICSs were crystalline. The content of each drug component in the powder was found to conform to the theoretical dose. The ternary powders generated high fine particle fractions (>50% of the loaded dose), with concomitant drug deposition on the impactor stages. The aerosol performance of B/F/M-SD was maintained after storage over silica gel at 22 degrees C for 11 weeks. In conclusion, co-spray dried particles of ICS/LABA/M-SD were largely crystalline, stable and showed excellent aerosol performance. They may provide an attractive alternative strategy to develop combination products without lactose blends. PMID:20172026

  16. The effects of exercise on dose and dose distribution of inhaled automotive pollutants

    SciTech Connect

    Kleinman, M.T.; Mautz, W.J. )

    1991-10-01

    The purpose of this study was to determine how changes in ventilation rate and in the entry route of air pollutants into the respiratory tract (nose versus mouth breathing) affected the respiratory tract uptake and penetration of inhaled gaseous and particulate pollutants associated with automobile emissions. Experiments were performed with female beagle dogs exposed while standing at rest or while exercising on a treadmill at 5 km/hour and a 7.5 percent grade. Dogs were exposed to nitrogen dioxide at concentrations of 1 and 5 parts per million (ppm), to formaldehyde at 2 and 10 ppm, and to an aerosol of ammonium nitrate particles (0.3 micron mass median aerodynamic diameter) at 1 mg/m3. Total respiratory system uptake and effects on breath time, expired tidal volume, fractional expiration time, minute ventilation, respiratory gas exchange, ventilation equivalents for oxygen and carbon dioxide, and dynamic pulmonary resistance and compliance were measured in exercising and resting dogs exposed for two hours to 5 ppm nitrogen dioxide and 10 ppm formaldehyde in combination with 1 mg/m3 of ammonium nitrate particles. Regional penetration of pollutants through oral and nasal airways and pollutant uptake in the lung were measured in a separate group of six tracheostomized dogs standing at rest while being exposed to nitrogen dioxide, formaldehyde, and ammonium nitrate particles. Hypercapnic stimulation was used to modify ventilation rates in the tracheostomized dogs while pollutant penetration and uptake were measured. Dogs exposed to 5 ppm of nitrogen dioxide at rest tended to breathe more rapidly (p less than 0.05) and more shallowly (a nonsignificant trend) than dogs exposed to purified air.

  17. Effects of long term inhaled high dose beclomethasone dipropionate on adrenal function.

    PubMed Central

    Smith, M J; Hodson, M E

    1983-01-01

    Studies of adrenal function were performed on 54 asthmatic patients who were taking long term high doses of inhaled beclomethasone dipropionate ranging from 500 to 2000 micrograms/day for between six and 60 months. Of the 43 patients taking up to 1500 micrograms/day, 39 (91%) had normal basal plasma cortisol concentrations and normal short tetracosactrin responses and 24 hour urinary free cortisol excretion was within the normal range in eight of nine patients tested. Some evidence of adrenal suppression was found in patients taking 2000 micrograms/day, with basal plasma cortisol below the normal range in four out of 11 patients and 24 hour urinary free cortisol excretion below the normal range in five out of six patients tested. Only one of the 11 patients taking 2000 micrograms/day had a short tetracosactrin response below the normal range: the mean rise in plasma cortisol was, however, significantly lower in this group than in those taking 1000 micrograms/day (328 (SE 30) and 506 (34) nmol/l respectively) (p less than 0.01). Patients taking more than 1500 micrograms/day of inhaled beclomethasone may require systemic corticosteroids during prolonged stress. PMID:6684806

  18. Effects of ramp-up of inspired airflow on in vitro aerosol dose delivery performance for certain dry powder inhalers.

    PubMed

    Ung, Keith T; Chan, Hak-Kim

    2016-03-10

    This study investigated the effect of airflow ramp-up on the dose delivery performance of seven dry powder inhalers, covering a broad range of powder formulations and powder dispersion mechanisms. In vitro performance tests were performed at a target pressure drop of 4kPa, using two inspiratory flow ramp-up conditions, representing slow and fast ramp-up of airflow, respectively. The fluidization of bulk powder and aerosol clearance from the inhaler was assessed by laser photometer evaluation of aerosol emission kinetics and measurement of the delivered dose (DD). The quality of aerosol dispersion (i.e. de-agglomeration) and associated lung targeting performance was assessed by measuring the total lung dose (TLD) using the Alberta idealized mouth-throat model. The ratio of DD and TLD under slow/fast ramp conditions was used as a metric to rank-order flow ramp effects. Test results show that the delivered dose is relatively unaffected by flow ramp (DD ratio ~1 for all dry powder inhalers). In contrast, the total lung dose showed significantly more variation as a function of flow ramp and inhaler type. Engineered (spray dried) powder formulations were associated with relatively high TLD (>50% of nominal dose) compared to lactose blend and agglomerate based formulations, which had a lower TLD (7-40% of nominal dose), indicative of less efficient targeting of the lung. The TLD for the Tobi Podhaler was the least influenced by flow ramp (TLD ratio ~1), while the TLD for the Asmanex Twisthaler was the most sensitive to flow ramp (TLD ratio ≪1). The relatively high sensitivity of the Asmanex Twisthaler to flow ramp is attributed to rapid aerosol clearance (from the inhaler) combined with a strong effect of flow-rate on particle de-agglomeration and resulting size distribution. PMID:26780380

  19. MDI: Mathematica database interface for the MFEDB

    SciTech Connect

    Wiley, J.C.; Miner, W.H. Jr.; Ross, D.W.

    1992-04-01

    We describe a new interface for the Magnetic Fusion Energy Database, MFEDB, which uses Mathematica{reg_sign} as a front end. MDI is a Mathematica package that defines a basic set of MFEDB access functions. The package will also accept standard SQL queries. Each function returns Mathematica-style lists, which can then be manipulated with any of the Mathematica functions. MDI also provides some utility functions for plotting and analyzing the data. The MDI package essentially makes the MFEDB an extension of Mathematica. The user may use any of the many Mathematica front-ends including telnet, X-Windows, or a notebook. The mdi.m package may be obtained by anonymous FTP from the MFEDB site or by use of netmfe, and E-mail database interface. MDI is a example of distributed computing. Behind the user interface, MDI calls an RPC client program that communicates with an RPC server on the MFEDB computer. It relies on the network communication capabilities of Mathematica to connect the user to a workstation running the Mathematica kernel. The Mathematica kernel is then connected to the MFEDB host workstation by a client/server pair of RPC processes. If the Mathematica kernel is to be run on the users` machine, the RPC client program must also be obtained and installed. The MDI RPC server is also available for users who would like to provide their own client software. The server returns ASCII tables from standards queries and may be accessed and processed by any program on the internet that has access to RPC services.

  20. MDI: Mathematica database interface for the MFEDB

    SciTech Connect

    Wiley, J.C.; Miner, W.H. Jr.; Ross, D.W.

    1992-04-01

    We describe a new interface for the Magnetic Fusion Energy Database, MFEDB, which uses Mathematica{reg sign} as a front end. MDI is a Mathematica package that defines a basic set of MFEDB access functions. The package will also accept standard SQL queries. Each function returns Mathematica-style lists, which can then be manipulated with any of the Mathematica functions. MDI also provides some utility functions for plotting and analyzing the data. The MDI package essentially makes the MFEDB an extension of Mathematica. The user may use any of the many Mathematica front-ends including telnet, X-Windows, or a notebook. The mdi.m package may be obtained by anonymous FTP from the MFEDB site or by use of netmfe, and E-mail database interface. MDI is a example of distributed computing. Behind the user interface, MDI calls an RPC client program that communicates with an RPC server on the MFEDB computer. It relies on the network communication capabilities of Mathematica to connect the user to a workstation running the Mathematica kernel. The Mathematica kernel is then connected to the MFEDB host workstation by a client/server pair of RPC processes. If the Mathematica kernel is to be run on the users' machine, the RPC client program must also be obtained and installed. The MDI RPC server is also available for users who would like to provide their own client software. The server returns ASCII tables from standards queries and may be accessed and processed by any program on the internet that has access to RPC services.

  1. Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models

    PubMed Central

    Lindert, Sandra; Below, Antje; Breitkreutz, Joerg

    2014-01-01

    The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®). Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15%) and pediatric (9%–11%) upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations. PMID:24514766

  2. PREDICTING THE ACUTE BEHAVIORAL EFFECTS OF TOLUENE INHALED FOR 24 HRS IN RATS: DOSE METRICS, METABOLISM AND BEHAVIORAL TOLERANCE

    EPA Science Inventory

    Purpose: Recent research on the acute effects of volatile organic compounds (VOCs) suggests that extrapolation from short (~ 1 h) to long durations (up to 4 h) is improved by using estimates of brain toluene concentration ( Br[ToI)] instead of cumulative inhaled dose (C x t) as a...

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

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

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

    PubMed Central

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

    2014-01-01

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

  6. Developing an in vitro understanding of patient experience with hydrofluoroalkane-metered dose inhalers.

    PubMed

    Doub, William H; Shah, Vibhakar; Limb, Susan; Guo, Changning; Liu, Xiaofei; Ngo, Diem

    2014-11-01

    As a result of the Montreal Protocol on Substances that Deplete the Ozone Layer, manufacturers of metered dose inhalers began reformulating their products to use hydrofluoroalkanes (HFAs) as propellants in place of chlorofluorocarbons (CFCs). Although the new products are considered safe and efficacious by the US Food and Drug Administration (FDA), a large number of complaints have been registered via the FDA's Adverse Events Reporting System (FAERS)-more than 7000 as of May 2013. To develop a better understanding of the measurable parameters that may, in part, determine in vitro performance and thus patient compliance, we compared several CFC- and HFA-based products with respect to their aerodynamic performance in response to changes in actuator cleaning interval and interactuation delay interval. Comparison metrics examined in this study were: total drug delivered ex-actuator, fine particle dose (<5 μm), mass median aerodynamic diameter, plume width, plume temperature, plume impaction force, and actuator orifice diameter. Overall, no single metric or test condition distinguishes HFA products from CFC products, but, for individual products tested, there were a combination of metrics that differentiated one from another. PMID:25228114

  7. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma

    PubMed Central

    Ducharme, Francine M; Ni Chroinin, Muireann; Greenstone, Ilana; Lasserson, Toby J

    2014-01-01

    Background In asthmatic patients inadequately controlled on inhaled corticosteroids and/or those with moderate persistent asthma, two main options are recommended: the combination of a long-acting inhaled ß2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids. Objectives To determine the effect of the combination of long-acting ß2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the risk of asthma exacerbations, pulmonary function and on other measures of asthma control, and to look for characteristics associated with greater benefit for either treatment option. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (MEDLINE, EMBASE and CINAHL), bibliographies of RCTs, clinical trial registries and correspondence with manufacturers until May 2008. Selection criteria RCTs that compared the combination of inhaled LABA and ICS to a higher dose of inhaled corticosteroids, in children and adults with asthma. Data collection and analysis Two authors independently assessed methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the number of patients experiencing one or more asthma exacerbations requiring oral corticosteroids. Main results This review included 48 studies (15,155 participants including 1155 children and 14,000 adults). Participants were inadequately controlled on their current ICS regimen, experiencing ongoing symptoms and with generally moderate (FEV1 60% to 79% of predicted) airway obstruction. The studies tested the combination of salmeterol or formoterol with a median dose of 400 mcg/day of beclomethasone or equivalent (BDP-eq) compared to a median of 1000 mcg/day of BDP-eq, usually for 24 weeks or less. There was a statistically significantly lower risk of exacerbations requiring systemic corticosteroids in patients treated with LABA and ICS

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

    PubMed

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

    2014-03-01

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

  9. Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

    PubMed Central

    Schell, Wiley A.; Bulmahn, Kenneth; Walton, Thomas E.; Woods, Christopher W.; Coghill, Catherine; Gallegos, Frank; Samore, Matthew H.; Adler, Frederick R.

    2013-01-01

    Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID50) of 11,000 spores (95% confidence interval 7,200–17,000), ID10 of 1,700 (1,100–2,600), and ID1 of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID50, 11.8 days (9.5–15.0) for ID10, and 12.1 days (9.9–15.3) for ID1. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses. PMID:24058320

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  11. Patient compliance with inhaled medication: does combining beta-agonists with corticosteroids improve compliance?

    PubMed

    Bosley, C M; Parry, D T; Cochrane, G M

    1994-03-01

    Patient compliance with an inhaled corticosteroid may be greater if it is combined with a beta-agonist. This study compared compliance with an inhaled corticosteroid (budesonide), and a short-acting inhaled beta-agonist (terbutaline sulphate), and a Turbuhaler inhaler containing a combination of the two drugs. In an open, multicentre, parallel group study 102 asthmatic patients were randomly divided into two groups, either receiving the two drugs in separate Turbuhalers or combined into one Turbuhaler. A twice daily regimen was prescribed and a preweighed metered-dose inhaler (MDI) of salbutamol was provided for rescue use. Compliance was measured using the Turbuhaler Inhalation Computer (TIC), which recorded the time and date of each inhalation over a 12 week period. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measurements were carried out at week 0, 6 and 12. Results from 72 patients were analysed. The average compliance was 60-70%. Treatment was taken as prescribed on 30-40% of the study days, and over-usage occurred on less than 10% of days. Only 15% of patients took the drugs as prescribed for more than 80% of the days. Compliance was no greater in patients using the combined inhalers. Other ways of improving patient self-management need further investigation. PMID:8013609

  12. Examining the importance of the particle size effect in inhalation dose assessment for short-term radiological events.

    PubMed

    Srimok, Boonchawee; Yim, Man-Sung

    2011-11-01

    In this research work, the question of how important the particle size effect is in assessing radiological impact from a short-term radiological dispersal device incident is examined. A computer model, called puff particle size-dependent inhalation dose assessment (PIDA), was developed to support the task. The PIDA code is composed of submodels for atmospheric transport, dry deposition, resuspension, human exposure and dose analysis, with the particle size effect explicitly described in all of the submodels. The time-dependent nature of contaminant transport in the atmosphere during a short-term radiological incident was described by using a three-dimensional dispersion and one-dimensional advection Gaussian puff model. The results from the PIDA code were found to be in reasonable agreement with the experimental data from the Prairie Grass Project under various stability conditions and also with the calculation results from the CALPUFF code. The use of the PIDA code to examine the particle size effect in a short-term radiological incident showed that the particle size is one of the key parameters that contribute to the uncertainty of the estimated inhalation dose. The results also indicated that ignoring the particle size effect typically results in a conservative estimate of inhalation dose. In this regard, the use of an appropriately selected fixed value for particle size could be acceptable for a conservative estimate. PMID:21156784

  13. Economics of "essential use exemptions" for metered-dose inhalers under the Montreal Protocol.

    PubMed

    DeCanio, Stephen J; Norman, Catherine S

    2007-10-01

    The Montreal Protocol on Substances that Deplete the Ozone Layer has led to rapid reductions in the use of ozone-depleting substances worldwide. However, the Protocol provides for "essential use exemptions" (EUEs) if there are no "technically and economically feasible" alternatives. An application that might qualify as an "essential use" is CFC-powered medical metered-dose inhalers (MDIs) for the treatment of asthma and chronic obstructive pulmonary disease (COPD), and the US and other nations have applied for exemptions in this case. One concern is that exemptions are necessary to ensure access to medications for low-income uninsureds. We examine the consequences of granting or withholding such exemptions, and conclude that government policies and private-sector programs are available that make it economically feasible to phase out chlorofluorocarbons (CFCs) in this application, thereby furthering the global public health objectives of the Montreal Protocol without compromising the treatment of patients who currently receive medication by means of MDIs. PMID:16982135

  14. Impact of the new nuclear decay data of ICRP publication 107 on inhalation dose coefficients for workers

    SciTech Connect

    Manabe, K.; Endo, Akira; Eckerman, Keith F

    2010-03-01

    The impact a revision of nuclear decay data had on dose coefficients was studied using data newly published in ICRP Publication 107 (ICRP 107) and existing data from ICRP Publication 38 (ICRP 38). Committed effective dose coefficients for occupational inhalation of radionuclides were calculated using two sets of decay data with the dose and risk calculation software DCAL for 90 elements, 774 nuclides and 1572 cases. The dose coefficients based on ICRP 107 increased by over 10 % compared with those based on ICRP 38 in 98 cases, and decreased by over 10 % in 54 cases. It was found that the differences in dose coefficients mainly originated from changes in the radiation energy emitted per nuclear transformation. In addition, revisions of the half-lives, radiation types and decay modes also resulted in changes in the dose coefficients.

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

    PubMed Central

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  17. 40 CFR 721.10299 - Polymeric MDI based polyurethanes (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymeric MDI based polyurethanes... Specific Chemical Substances § 721.10299 Polymeric MDI based polyurethanes (generic). (a) Chemical... as polymeric MDI based polyurethanes (PMNs P-00-2, P-00-5, and P-00-6) are subject to reporting...

  18. 40 CFR 721.10299 - Polymeric MDI based polyurethanes (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymeric MDI based polyurethanes... Specific Chemical Substances § 721.10299 Polymeric MDI based polyurethanes (generic). (a) Chemical... as polymeric MDI based polyurethanes (PMNs P-00-2, P-00-5, and P-00-6) are subject to reporting...

  19. 40 CFR 721.10299 - Polymeric MDI based polyurethanes (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymeric MDI based polyurethanes... Specific Chemical Substances § 721.10299 Polymeric MDI based polyurethanes (generic). (a) Chemical... as polymeric MDI based polyurethanes (PMNs P-00-2, P-00-5, and P-00-6) are subject to reporting...

  20. Using smartphone as a motion detector to collect time-microenvironment data for estimating the inhalation dose.

    PubMed

    Hoi, Tran Xuan; Phuong, Huynh Truc; Van Hung, Nguyen

    2016-09-01

    During the production of iodine-131 from neutron irradiated tellurium dioxide by the dry distillation, a considerable amount of (131)I vapor is dispersed to the indoor air. People who routinely work at the production area may result in a significant risk of exposure to chronic intake by inhaled (131)I. This study aims to estimate the inhalation dose for individuals manipulating the (131)I at a radioisotope production. By using an application installed on smartphones, we collected the time-microenvironment data spent by a radiation group during work days in 2015. Simultaneously, we used a portable air sampler combined with radioiodine cartridges for grabbing the indoor air samples and then the daily averaged (131)I concentration was calculated. Finally, the time-microenvironment data jointed with the concentration to estimate the inhalation dose for the workers. The result showed that most of the workers had the annual internal dose in 1÷6mSv. We concluded that using smartphone as a motion detector is a possible and reliable way instead of the questionnaires, diary or GPS-based method. It is, however, only suitable for monitoring on fixed indoor environments and limited the targeted people. PMID:27451110

  1. Radiation-dose estimates and hazard evaluations for inhaled airborne radionuclides. Annual progress report, July 1981-June 1982

    SciTech Connect

    Mewhinney, J.A.

    1983-06-01

    The objective was to conduct confirmatory research on aerosol characteristics and the resulting radiation dose distribution in animals following inhalation and to provide prediction of health consequences in humans due to airborne radioactivity which might be released in normal operations or under accident conditions during production of nuclear fuel composed of mixed oxides of U and Pu. Four research reports summarize the results of specific areas of research. The first paper details development of a method for determination of specific surface area of small samples of mixed oxide or pure PuO/sub 2/ particles. The second paper details the extension of the biomathematical model previously used to describe retention, distribution and excretion of Pu from these mixed oxide aerosols to include a description of Am and U components of these aerosols. The third paper summarizes the biological responses observed in radiation dose pattern studies in which dogs, monkeys and rate received inhalation exposures to either 750/sup 0/C heat treated UO/sub 2/ + PuO/sub 2/, 1750/sup 0/C heat-treated (U,Pu)O/sub 2/ or 850/sup 0/C heat-treated pure PuO/sub 2/. The fourth paper described dose-response studies in which rats were exposed to (U,Pu)O/sub 2/ or pure PuO/sub 2/. This paper updates earlier reports and summarizes the status of animals through approximately 650 days after inhalation.

  2. Dose-dependent onset and cessation of action of inhaled budesonide on exhaled nitric oxide and symptoms in mild asthma

    PubMed Central

    Kharitonov, S; Donnelly, L; Montuschi, P; Corradi, M; Collins, J; Barnes, P

    2002-01-01

    Background: Dose dependent anti-inflammatory effects of inhaled corticosteroids in asthma are difficult to demonstrate in clinical practice. The anti-inflammatory effect of low dose inhaled budesonide on non-invasive exhaled markers of inflammation and oxidative stress were assessed in patients with mild asthma. Methods: 28 patients entered a double blind, placebo controlled, parallel group study and were randomly given either 100 or 400 µg budesonide or placebo once daily, inhaled from a dry powder inhaler (Turbohaler), for 3 weeks followed by 1 week without treatment. Exhaled nitric oxide (NO), exhaled carbon monoxide (CO), nitrite/nitrate, S-nitrosothiols, and 8-isoprostanes in exhaled breath condensate were measured four times during weeks 1 and 4, and once a week during weeks 2 and 3. Results: A dose-dependent speed of onset and cessation of action of budesonide was seen on exhaled NO and asthma symptoms. Treatment with 400 µg/day reduced exhaled NO faster (–2.06 (0.37) ppb/day) than 100 µg/day (–0.51 (0.35) ppb/day; p<0.01). The mean difference between the effect of 100 and 400 µg budesonide was –1.55 ppb/day (95% CI –2.50 to –0.60). Pretreatment NO levels were positively related to the subsequent speed of reduction during the first 3–5 days of treatment. Faster recovery of exhaled NO was seen after stopping treatment with budesonide 400 µg/day (1.89 (1.43) ppb/day) than 100 µg/day (0.49 (0.34) ppb/day, p<0.01). The mean difference between the effect of 100 and 400 µg budesonide was 1.40 ppb/day (95% CI –0.49 to 2.31). Symptom improvement was dose-dependent, although symptoms returned faster in patients treated with 400 µg/day. A significant reduction in exhaled nitrite/nitrate and S-nitrosothiols after budesonide treatment was not dose-dependent. There were no significant changes in exhaled CO or 8-isoprostanes in breath condensate. Conclusion: Measurement of exhaled NO levels can indicate a dose-dependent onset and cessation of anti

  3. Biomarkers of Dose and Effect of Inhaled Ozone in Resting versus Exercising Human Subjects: Comparison with Resting Rats

    PubMed Central

    Hatch, Gary E.; McKee, John; Brown, James; McDonnell, William; Seal, Elston; Soukup, Joleen; Slade, Ralph; Crissman, Kay; Devlin, Robert

    2013-01-01

    To determine the influence of exercise on pulmonary dose of inhaled pollutants, we compared biomarkers of inhaled ozone (O3) dose and toxic effect between exercise levels in humans, and between humans and rats. Resting human subjects were exposed to labeled O3 (18O3, 0.4 ppm, for 2 hours) and alveolar O3 dose measured as the concentration of excess 18O in cells and extracellular material of nasal, bronchial, and bronchoalveolar lavage fluid (BALF). We related O3 dose to effects (changes in BALF protein, LDH, IL-6, and antioxidant substances) measurable in the BALF. A parallel study of resting subjects examined lung function (FEV1) changes following O3. Subjects exposed while resting had 18O concentrations in BALF cells that were 1/5th of those of exercising subjects and directly proportional to the amount of O3 breathed during exposure. Quantitative measures of alveolar O3 dose and toxicity that were observed previously in exercising subjects were greatly reduced or non-observable in O3 exposed resting subjects. Resting rats and resting humans were found to have a similar alveolar O3 dose. PMID:23761957

  4. Inhalation reference dose (RfDi): An application of interspecies dosimetry modeling for risk assessment of insoluble particles

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, H.; Dourson, M.L.; Miller, F.J.

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of the methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. The paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

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

    PubMed Central

    Ram, Felix SF; Carvallho, Celso R; White, John

    2011-01-01

    Objectives: Medication for the management of chronic obstructive pulmonary disease (COPD) may be delivered by a number of different inhaler devices. This study was undertaken to determine the clinical effectiveness of the Respimat® handheld inhaler device compared with other handheld inhaler devices for the delivery of medication in stable COPD. Methodology: A systematic review of high-quality randomized controlled clinical trials comparing Respimat with other inhaler devices using the same medication was performed. Studies were searched for in the Cochrane Central Register of Controlled Trials as well as other relevant electronic databases. Manufacturers of inhaled COPD medication were also contacted for potential trials. Results: Seven studies of high methodological quality with 3813 participants were included in the review. Three trials used Handihaler® as the comparator inhaler, three used a chlorofluorocarbon metered-dose inhaler (CFC-MDI), and one trial used a hydroflouroalkane (HFA)-MDI. When Respimat was compared with Handihaler, the following reported outcomes were not significantly different: trough forced expiratory volume in 1 second (FEV1) (weighted mean difference [WMD] 0.01 L; P = 0.14), trough forced vital capacity (FVC) (WMD 0.001 L: P = 0.88), peak FEV1 (WMD 0.01 L: P = 0.08), peak FVC (WMD 0.01 L: P = 0.55), morning peak expiratory flow rate (PEFR) (WMD 5.06 L/min: P = 0.08), and evening PEFR (WMD 4.39 L/min: P = 0.15). Furthermore, there were no differences when Respimat was compared with Handihaler for risk of exacerbations (relative risk [RR] 0.94: P = 0.81), dry mouth (RR 1.57: P = 0.34), or nasopharyngitis (RR 1.42: P = 0.22). For Respimat compared with CFC-MDI, the 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

  6. Single-dose and steady-state pharmacokinetic and pharmacodynamic evaluation of therapeutically clinically equivalent doses of inhaled fluticasone propionate and budesonide, given as Diskus or Turbohaler dry-powder inhalers to healthy subjects.

    PubMed

    Möllmann, H; Wagner, M; Krishnaswami, S; Dimova, H; Tang, Y; Falcoz, C; Daley-Yates, P T; Krieg, M; Stöckmann, R; Barth, J; Lawlor, C; Möllmann, A C; Derendorf, H; Hochhaus, G

    2001-12-01

    Direct comparisons of the pharmacokinetic (PK) and systemic pharmacodynamic (PD) properties of inhaled corticosteroids after single and multiple dosing in the same subjects are scarce. The objective of this study was to compare thePK/PDproperties of clinically equivalent, single, and multiple doses of dry-powder formulations of inhaled fluticasone propionate (FP 200 and 500 microg via Diskus) and budesonide (BUD, 400 and 1,000 microg via Turbohaler). Fourteen healthy subjects completed a double-blind, double-dummy, randomized, placebo-controlled, five-way crossover study consisting of a single dose administered at 8 a.m. on day 1 followed by 4 days of twice-daily dosing at 8 a.m. and 8 p.m. on days 2 to 5. Serum concentrations of FP and BUD were measured using validated liquid chromatography/ mass spectrometry assays. The 24-hour cumulative cortisol suppression (CCS) in serum was monitored as the pharmacodynamic surrogate marker. Peak serum concentrations following single and multiple dosing were observed 10 to 30 minutes after inhalation for BUD and 30 to 90 minutes afterinhalation of FP with no influence of dose ordosingregimen. After a single dose of 1000 microg BUD and 500 microg FP the median estimates of terminal half-life and mean residence time were 3.5 and 3.9 hours for BUD and 10.1 and 12.0 hours for FP, respectively. Using previously reported intravenous data, the mean absorption times (MAT) were calculated to be around 2 hours and 7 hours for BUD and FP respectively. On average, the area under the curve (A UC) at steady state (day 5) was up to 30% higher for BUD compared to that over a 12-hour period following the first dose on day 1, whereas A UC estimates were 50% to 80% higherforFP at steady state, indicating accumulation. However, the steady-state Cmax values were seven to eight times and AUC values three to four times higher for BUD than for FP. Comparison of active treatment data with placebo showed that CCS after a single dose was not pronounced

  7. Modeling Deposition of Inhaled Particles

    EPA Science Inventory

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

  8. LOW-DOSE AIRBORNE ENDOTOXIN EXPOSURE ENHANCES BRONCHIAL RESPONSIVENESS TO INHALED ALLERGEN IN ATOPIC ASTHMATICS

    EPA Science Inventory

    Endotoxin exposure has been associated with both protection against development of TH2-immune responses during childhood and exacerbation of asthma in persons who already have allergic airway inflammation.1 Occupational and experimental inhalation exposures to endotoxin have been...

  9. Airflows after inhalation of terbutaline sulphate aerosol from a 750-ml spacer for four weeks.

    PubMed

    Eriksson, N E; Hidinger, K G; Rosenhall, L; Hagstad, H; Löfgren, L; Perk, J; Stiksa, G; Ström, K

    1986-01-01

    Terbutaline sulphate was administered to 40 adult asthmatic patients via an ordinary metered-dose inhaler (MDI) or one connected to a 750-ml spacer in an open, randomized, crossover study. Spirometry was obtained before the start of the study and again after four weeks of treatment with each inhaler. The patients recorded on a diary card the severity of their asthma symptoms and the peak expiratory flow rate (PEFR) in the morning before and after drug administration and in the evening. Preinhalation spirometric values were higher after four weeks with the 750-ml spacer than at the start of the study (P less than or equal to 0.05). Daily morning and evening PEFR values were higher after use of the 750-ml spacer than after use of the ordinary MDI (P less than 0.05). Daily symptom scores were generally low. A significantly better effect (P less than or equal to 0.05) with the 750-ml spacer was achieved only in daytime dyspnea. The investigators conclude that the attachment of a 750-ml spacer to an ordinary metered-dose inhaler can improve the efficacy of terbutaline sulphate in the long-term treatment of asthma. PMID:3698068

  10. [A new fixed dose combination of fluticasone and formoterol in a pressurised metered-dose inhaler for the treatment of asthma].

    PubMed

    Devillier, P; Salvator, H; Grassin-Delyle, S; Naline, E; Advenier, C; Roche, N

    2014-10-01

    The combination of an inhaled corticosteroid and a long acting beta-2 agonist is indicated for the regular treatment of persistent moderate-to-severe asthmatics whose asthma is not controlled by inhaled corticosteroids and the occasional use of a short acting beta-2 agonist. The aim of this review is to give an overview of the rationale of combining formoterol and fluticasone and to analyze the clinical data concerning a new fixed combination of fluticasone and formoterol in a pressurised metered-dose inhaler with a dose counter (Flutiform(®)) that was approved for the treatment of asthma in France in 2013. The clinical studies provide evidence that combined fluticasone/formoterol is more efficacious than fluticasone or formoterol given alone, and provides similar improvements in lung function to fluticasone (Flixotide(®)) and formoterol (Foradil(®)) administered concurrently. The combination of fluticasone/formoterol gave a more rapid bronchodilatation than the combination fluticasone/salmeterol. As a whole, the combination of fluticasone/formoterol had similar efficacy and tolerability profiles to the combinations of either budesonide/formoterol or fluticasone/salmeterol. PMID:25391505

  11. Age-dependent inhalation doses to members of the public from indoor short-lived radon progeny.

    PubMed

    Brudecki, K; Li, W B; Meisenberg, O; Tschiersch, J; Hoeschen, C; Oeh, U

    2014-08-01

    The main contribution of radiation dose to the human lungs from natural exposure originates from short-lived radon progeny. In the present work, the inhalation doses from indoor short-lived radon progeny, i.e., (218)Po, (214)Pb, (214)Bi, and (214)Po, to different age groups of members of the public were calculated. In the calculations, the age-dependent systemic biokinetic models of polonium, bismuth, and lead published by the International Commission on Radiological Protection (ICRP) were adopted. In addition, the ICRP human respiratory tract and gastrointestinal tract models were applied to determine the deposition fractions in different regions of the lungs during inhalation and exhalation, and the absorption fractions of radon progeny in the alimentary tract. Based on the calculated contribution of each progeny to equivalent dose and effective dose, the dose conversion factor was estimated, taking into account the unattached fraction of aerosols, attached aerosols in the nucleation, accumulation and coarse modes, and the potential alpha energy concentration fraction in indoor air. It turned out that for each progeny, the equivalent doses to extrathoracic airways and the lungs are greater than those to other organs. The contribution of (214)Po to effective dose is much smaller compared to that of the other short-lived radon progeny and can thus be neglected in the dose assessment. In fact, 90 % of the effective dose from short-lived radon progeny arises from (214)Pb and (214)Bi, while the rest is from (218)Po. The dose conversion factors obtained in the present study are 17 and 18 mSv per working level month (WLM) for adult female and male, respectively. This compares to values ranging from 6 to 20 mSv WLM(-1) calculated by other investigators. The dose coefficients of each radon progeny calculated in the present study can be used to estimate the radiation doses for the population, especially for small children and women, in specific regions of the world

  12. Low-dose inhaled nitric oxide in term and near-term infants with hypoxic respiratory failure: a Malaysian experience.

    PubMed

    Goh, A Y; Lum, L C; Roziah, M

    2001-09-01

    Inhaled nitric oxide (iNO) improves oxygenation in term and near-term infants with persistent pulmonary hypertension of the newborn (PPHN) and decreases the need for treatment with extracorporeal membrane oxygenation (ECMO). This mode of treatment is currently being introduced in Malaysia. We report our preliminary experience using low dose inhaled nitric oxide (20 parts per million) in three newborn infants (meconium aspiration syndrome, primary PPHN and congenital diaphragmatic hernia) with severe PPHN who fulfilled criteria for ECMO with a mean oxygenation index (OI) of 40. Two of the infants showed rapid and sustained improvement in oxygenation with a reduction in oxygenation index (OI) over 24 hours. The infant with diaphragmatic hernia showed an initial improvement in OI, which was unsustained and subsequently died. All three infants did not show significant elevation of methemoglobin or nitrogen dioxide (NO2). Inhaled nitric oxide is an effective and safe treatment for severe PPHN that can be used in a developing country like Malaysia. PMID:11732080

  13. DEVELOPMENT OF A DOSE-RESPONSE MODEL FOR INHALED B[A]P

    EPA Science Inventory

    This report analyzes the tumor data from the hamster inhalation bioassay of B[a]P conducted by Thyssen et al. (1981). etailed data on the incidence of laryngeal and pharyngeal tumors and chamber B[a]P concentration had been obtained by the authors in a previous contract (EPA 68-0...

  14. Argon Inhalation Attenuates Retinal Apoptosis after Ischemia/Reperfusion Injury in a Time- and Dose-Dependent Manner in Rats

    PubMed Central

    Ulbrich, Felix; Schallner, Nils; Coburn, Mark; Loop, Torsten; Lagrèze, Wolf Alexander; Biermann, Julia; Goebel, Ulrich

    2014-01-01

    Purpose Retinal ischemia and reperfusion injuries (IRI) permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC) of the rat's eye. Methods IRI was performed on the left eyes of rats (n = 8) with or without inhaled Argon postconditioning (25, 50 and 75 Vol%) for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours). Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA. Results IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001). Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01), as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001). Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%. Conclusion Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option. PMID

  15. Continuous low dose inhaled nitric oxide for treatment of severe pulmonary hypertension after cardiac surgery in paediatric patients.

    PubMed Central

    Beghetti, M.; Habre, W.; Friedli, B.; Berner, M.

    1995-01-01

    OBJECTIVE--To assess the effect of inhaled nitric oxide (NO) on severe postoperative pulmonary hypertension in children after surgical repair of a congenital heart defect. DESIGN--A pilot study of NO administration to 7 consecutive children who required adrenergic support and in whom postoperative mean pulmonary artery pressure was more than two thirds of mean systemic pressure and persisted despite alkalotic hyperventilation. SETTING--Routine care after cardiac surgery for congenital heart disease in a multidisciplinary paediatric intensive care unit. METHODS--Continuous inhalation of NO, initially at 15 ppm. Therefore, daily attempts at complete weaning or at reducing NO to the lowest effective dose. RESULTS--In 6 of the 7 children NO inhalation selectively decreased mean (SD) pulmonary artery pressure from 51 (12) to 31 (9) mm Hg (P < 0.05) while mean systemic arterial pressure was unchanged (68 (10) v 71 (7) mm Hg) (NS) and the arteriovenous difference in oxygen content decreased from 6.7 (0.9) to 4.8 (0.8) vol% (P < 0.05). Concomitantly PaO2 increased from 158 (98) to 231 (79) mm Hg) (P < 0.05). The seventh child showed no response to NO up to 80 ppm, could not be weaned from cardiopulmonary bypass, and died in the operating room. In responders, attempts at early weaning from NO inhalation always failed and NO at concentrations of less than 10 ppm was continuously administered for a median of 9.5 days (range 4 to 16 days) until complete weaning was possible from a mean dose of 3.9 (2.9) ppm. Methaemoglobinaemia remained below 2% and nitrogen dioxide concentrations usually ranged from 0.1 to 0.2 ppm. One child later died and five were discharged. A few months after surgery Doppler echocardiography (and catheterisation in one) showed evidence of regression of pulmonary hypertension in all 5. CONCLUSIONS--Inhalation of NO reduced pulmonary artery pressure in children with severe pulmonary hypertension after cardiac surgery and this effect was maintained over

  16. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation

    PubMed Central

    Kataoka, Takahiro

    2013-01-01

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. PMID:23420683

  17. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation.

    PubMed

    Kataoka, Takahiro

    2013-07-01

    Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation. PMID:23420683

  18. Improved SOLA Inversions of MDI Data

    NASA Astrophysics Data System (ADS)

    Larsen, R. M.; Christensen-Dalsgaard, J.; Kosovichev, A. G.; Schou, J.

    We present a new version of 2d-SOLA, where the target functions have been modified to match the behavior of the mode kernels near the rotation axis and to minimize near-surface contributions. Inversion of artificial data show that these modifications significantly improve the effective resolution near the pole, which allows us to assess the reliability of the high-latitude features seen by other inversion methods. Most importantly, our new inversions seem to confirm the detection of a submerged polar jet previously seen in the 2d-RLS inversions reported by Schou et al. 1998. A test of the robustness of the improved method is carried out by inverting artificial data from the MDI Hare and Hounds exercise. We analyze the averaging kernels and error propagation of the method, and also describe the error-correlation between different points in the solution, the latter being a potential source of spurious features in the solutions as pointed out by Howe and Thompson, 1996. So far, helioseismic datasets given in the form of a-coefficients have been inverted under the assumption that the errors in different a-coefficients are uncorrelated. The MDI peak-bagging procedure, however, does produce estimates of the error-correlation between a-coefficients within the same multiplet. Here we investigate the effect of including this knowledge in the inversions.

  19. A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes.

    PubMed

    Simpson, A J; Bood, J R; Anderson, S D; Romer, L M; Dahlén, B; Dahlén, S-E; Kippelen, P

    2016-05-01

    Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled β2-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11β-prostaglandin F2α (11β-PGF2α). The maximum fall in forced expiratory volume in 1 s of 14 (12-20)% (median and interquartile range) following placebo was attenuated to 7 (5-9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11β-PGF2α from 41 (27-57) ng/mmol creatinine at baseline to 58 (43-72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11β-PGF2α was inhibited with administration of terbutaline: 39 (28-44) ng/mmol creatinine at baseline vs. 40 (33-58) ng/mmol creatinine at its peak post-EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB. PMID:26846550

  20. A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes

    PubMed Central

    Simpson, A. J.; Bood, J. R.; Anderson, S. D.; Romer, L. M.; Dahlén, B.; Dahlén, S.-E.

    2016-01-01

    Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled β2-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11β-prostaglandin F2α (11β-PGF2α). The maximum fall in forced expiratory volume in 1 s of 14 (12–20)% (median and interquartile range) following placebo was attenuated to 7 (5–9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11β-PGF2α from 41 (27–57) ng/mmol creatinine at baseline to 58 (43–72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11β-PGF2α was inhibited with administration of terbutaline: 39 (28–44) ng/mmol creatinine at baseline vs. 40 (33–58) ng/mmol creatinine at its peak post-EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB. PMID:26846550

  1. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children

    PubMed Central

    Ducharme, Francine M; Ni Chroinin, Muireann; Greenstone, Ilana; Lasserson, Toby J

    2014-01-01

    Background Long-acting inhaled ß2-adrenergic agonists (LABAs) are recommended as ’add-on’ medication to inhaled corticosteroids (ICS) in the maintenance therapy of asthmatic adults and children aged two years and above. Objectives To quantify in asthmatic patients the safety and efficacy of the addition of LABAs to ICS in patients insufficiently controlled on ICS alone. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until May 2008. Selection criteria We included RCTs if they compared the addition of inhaled LABAs versus placebo to the same dose of ICS in children aged two years and above and in adults. Data collection and analysis Two review authors independently assessed studies for methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the relative risk (RR) of asthma exacerbations requiring rescue oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), rescue beta2-agonist use, symptoms, withdrawals and adverse events. Main results Seventy-seven studies met the entry criteria and randomised 21,248 participants (4625 children and 16,623 adults). Participants were generally symptomatic at baseline with moderate airway obstruction despite their current ICS regimen. Formoterol or salmeterol were most frequently added to low-dose ICS (200 to 400 μg/day of beclomethasone (BDP) or equivalent) in 49% of the studies. The addition of a daily LABA to ICS reduced the risk of exacerbations requiring oral steroids by 23% from 15% to 11% (RR 0.77, 95% CI 0.68 to 0.87, 28 studies, 6808 participants). The number needed to treat with the addition of LABA to prevent one use of rescue oral corticosteroids is 41 (29, 72), although the event rates in the ICS groups varied between 0% and

  2. Inhalation and ingestion intakes with associated dose estimates for level II and level III personnel using Capstone study data.

    PubMed

    Szrom, Frances; Falo, Gerald A; Lodde, Gordon M; Parkhurst, Mary Ann; Daxon, Eric G

    2009-03-01

    Depleted uranium (DU) intake rates and subsequent dose rates were estimated for personnel entering armored combat vehicles perforated with DU penetrators (level II and level III personnel) using data generated during the Capstone DU Aerosol Study. Inhalation intake rates and associated dose rates were estimated from cascade impactors worn by sample recovery personnel and from cascade impactors that served as area monitors. Ingestion intake rates and associated dose rates were estimated from cotton gloves worn by sample recovery personnel and from wipe-tests samples from the interior of vehicles perforated with large-caliber DU munitions. The mean DU inhalation intake rate for level II personnel ranged from 0.447 mg h(-1) based on breathing zone monitor data (in and around a perforated vehicle) to 14.5 mg h(-1) based on area monitor data (in a perforated vehicle). The mean DU ingestion intake rate for level II ranged from 4.8 mg h(-1) to 38.9 mg h(-1) based on the wipe-tests data including surface-to-glove transfer factors derived from the Capstone data. Based on glove contamination data, the mean DU ingestion intake rates for level II and level III personnel were 10.6 mg h(-1) and 1.78 mg h(-1), respectively. Effective dose rates and peak kidney uranium concentration rates were calculated based on the intake rates. The peak kidney uranium concentration rate cannot be multiplied by the total exposure duration when multiple intakes occur because uranium will clear from the kidney between the exposures. PMID:19204492

  3. Inhalation and Ingestion Intakes with Associated Dose Estimates for Level II and Level III Personnel Using Capstone Study Data

    SciTech Connect

    Szrom, Fran; Falo, Gerald A.; Lodde, Gordon M.; Parkhurst, MaryAnn; Daxon, Eric G.

    2009-03-01

    Depleted uranium (DU) intake rates and subsequent dose rates were estimated for personnel entering armored combat vehicles perforated with DU penetrators (level II and level III personnel) using data generated during the Capstone Depleted Uranium (DU) Aerosol Study. Inhalation intake rates and associated dose rates were estimated from cascade impactors worn by sample recovery personnel and from cascade impactors that served as area monitors. Ingestion intake rates and associated dose rates were estimated from cotton gloves worn by sample recovery personnel and from wipe test samples from the interior of vehicles perforated with large caliber DU munitions. The mean DU inhalation intake rate for level II personnel ranged from 0.447 mg h-1 based on breathing zone monitor data (in and around a perforated vehicle) to 14.5 mg h-1 based on area monitor data (in a perforated vehicle). The mean DU ingestion intake rate for level II ranged from 4.8 mg h-1 to 38.9 mg h-1 based on the wipe test data including surface to glove transfer factors derived from the Capstone data. Based on glove contamination data, the mean DU ingestion intake rates for level II and level III personnel were 10.6 mg h-1 was and 1.78 mg h-1, respectively. Effective dose rates and peak kidney uranium concentration rates were calculated based on the intake rates. The peak kidney uranium concentration rate cannot be multiplied by the total exposure duration when multiple intakes occur because uranium will clear from the kidney between the exposures.

  4. Carcinogenesis From Inhaled (PuO2)-Pu-239 in Beagles: Evidence for Radiation Homeostasis at Low Doses?

    SciTech Connect

    Fisher, Darrell R.; Weller, Richard E.

    2010-09-01

    From the early 1970s to the late 1980s, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium (239PuO2, 238PuO2, and 239Pu[NO3]4) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study is to reassess the dose-response relationship for lung cancer induction in the 239PuO2 dogs compared to controls, with particular focus on the dose-response at low lung doses. A 239PuO2 aerosol (2.3 μm AMAD, 1.9 μm GSD) was administered to six groups of 20 young (18-month old) beagle dogs (10 males and 10 females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 ± 48 Bq (3.5 ± 1.3 nCi), corresponding to 1 Bq g-1 lung tissue (0.029 ± 0.001 nCi g-1. Groups 2 through 6 received initial lung depositions (mean values) of 760, 2724, 10345, 37900, and 200000 Bq (22, 79, 300, 1100, and 5800 nCi) 239PuO2, respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, epidermoid carcinoma) and radiation pneumonitis (highest exposures group) was observed in dogs exposed to 239PuO2. Calculated lung doses ranged from a few cGy in early-sacrificed dogs to 7764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. Lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 ± 7.6 c

  5. Development of Room Temperature Stable Formulation of Formoterol Fumarate/Beclomethasone HFA pMDI

    PubMed Central

    Purohit, D.; Trehan, A.; Arora, V.

    2009-01-01

    The primary aim of present investigation was to develop and formulate room temperature stable formulation of formoterol fumarate and beclomethasone dipropionate with extra fine part size of hydrofluoroalkane pressurized metered dose inhalers. Particle size distribution of hydrofluoroalkane pressurized metered dose inhalers was evaluated using Twin Stage Glass Impinger and Anderson Cascade Impactor. A tetrafluoroethane and/or heptafluoropropane were evaluated for preparation of hydrofluoroalkane pressurized metered dose inhalers. The fine particle fractions delivered from hydrofluoroalkane propellant suspension pressurized metered dose inhalers can be predicted on the basis of formulation parameters and is dependent of metering chamber of valve and orifice size of actuators. The results presented in investigation showed the importance of formulation excipients with formulation of pressurized metered dose inhalers viz, canister, valve and actuators used in formulations.

  6. Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

    PubMed Central

    2014-01-01

    Background The increased production of nanomaterials has caused a corresponding increase in concern about human exposures in consumer and occupational settings. Studies in rodents have evaluated dose–response relationships following respiratory tract (RT) delivery of nanoparticles (NPs) in order to identify potential hazards. However, these studies often use bolus methods that deliver NPs at high dose rates that do not reflect real world exposures and do not measure the actual deposited dose of NPs. We hypothesize that the delivered dose rate is a key determinant of the inflammatory response in the RT when the deposited dose is constant. Methods F-344 rats were exposed to the same deposited doses of titanium dioxide (TiO2) NPs by single or repeated high dose rate intratracheal instillation or low dose rate whole body aerosol inhalation. Controls were exposed to saline or filtered air. Bronchoalveolar lavage fluid (BALF) neutrophils, biochemical parameters and inflammatory mediator release were quantified 4, 8, and 24 hr and 7 days after exposure. Results Although the initial lung burdens of TiO2 were the same between the two methods, instillation resulted in greater short term retention than inhalation. There was a statistically significant increase in BALF neutrophils at 4, 8 and 24 hr after the single high dose TiO2 instillation compared to saline controls and to TiO2 inhalation, whereas TiO2 inhalation resulted in a modest, yet significant, increase in BALF neutrophils 24 hr after exposure. The acute inflammatory response following instillation was driven primarily by monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, mainly within the lung. Increases in heme oxygenase-1 in the lung were also higher following instillation than inhalation. TiO2 inhalation resulted in few time dependent changes in the inflammatory mediator release. The single low dose and repeated exposure scenarios had similar BALF cellular and mediator response trends

  7. The technology of metered-dose inhalers and treatment costs in asthma: a retrospective study of breath actuation versus traditional press-and-breathe inhalers.

    PubMed

    Langley, P C

    1999-01-01

    This paper reviews the impact of the use of technologically dissimilar beta-agonist aerosols--the Maxair Autohaler (pirbuterol acetate) breath-actuated aerosol and the traditional albuterol press-and-breathe inhaler-on the treatment costs of asthma. If, as clinical evidence would suggest, the breath-actuated aerosol is not only as effective as an albuterol inhaler with a spacer, but is easier to use and results in more optimal beta-agonist use by patients, then one might consider the hypothesis that patients possessing a breath-actuated inhaler would, ceteris paribus, experience lower asthma-related treatment costs-principally, those medical costs associated with fewer emergency room visits and hospitalizations. This hypothesis is considered from the perspective of a retrospective claims database study of patients who used one or the other beta-agonist inhaler exclusively. At the descriptive level, costs of treatment for patients using the press-and-breathe inhaler are estimated to be 16.5% greater than costs for patients using the breath-actuated inhaler. In the multivariate analysis, the presence of the breath-actuated inhaler (in a dummy variable analysis) was not only statistically significant (P < 0.05), but entered with the expected negative sign. Estimated cost impacts under various model specifications are consistent with the magnitude of the cost differences reported in the descriptive analysis. Total cost savings with the Maxair Autohaler ranged from 8.7% to 11.7%, with medical cost savings estimated at 14.6%. PMID:10090438

  8. Albuterol Oral Inhalation

    MedlinePlus

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

  9. Pulmonary carcinogenicity of relatively low doses of beta-particle radiation from inhaled 144CeO2 in rats.

    PubMed

    Lundgren, D L; Hahn, F F; Griffith, W C; Hubbs, A F; Nikula, K J; Newton, G J; Cuddihy, R G; Boecker, B B

    1996-11-01

    This study was conducted to examine the carcinogenic effects of inhaled beta-particle-emitting radionuclides, particularly in lower dose regions in which there were substantial uncertainties associated with available information. A total of 2751 F344/N rats (1358 males and 1393 females) approximately 12 weeks of age at exposure were used. Of these, 1059 rats were exposed to aerosols of 144CeO2 to achieve mean desired initial lung burdens (ILBs) of 18 kBq (low level), 247 rats to achieve mean ILBs of 60 kBq (medium level) and 381 rats to achieve mean ILBs of 180 kBq (high level). Control rats (total of 1064) were exposed to aerosols of stable CeO2. Based on the 95% confidence intervals of the median survival times and the cumulative survival curves, there were no significant differences in the survival of groups of female and male exposed rats relative to controls. The mean lifetime beta-particle doses to the lungs of the rats in the four groups were: low level, 3.6 +/- 1.3 (+/-SD) Gy; medium level, 12 +/- 4.5 Gy; and high level, 37 +/- 5.9 Gy. The crude incidence of lung neoplasms increased linearly with increasing doses to the lungs (controls, 0.57%; low level, 2.0%; medium level, 6.1%; and high level, 19%). The estimated linear risk coefficients for lung neoplasms per unit of dose to the lung were not significantly different for the three dose levels studied. The risk coefficient at the lower level was 39 +/- 14 (+/-SE) excess lung neoplasms per 10(4) rat Gy; at the medium level the risk was 47 +/- 12; and at the higher level the risk was 50 +/- 9.0. The relationship of beta-particle dose to the lung and the crude incidence of lung neoplasms was described adequately by a linear function. We concluded that the risk of lung neoplasms in rats per unit of radiation dose did not increase with decreasing mean beta-particle dose to the lung over the range of 3.6 to 37 Gy. The weighted average of these three values was 47 +/- 6.4 (+/-SE) excess lung neoplasms per 10

  10. About Steroids (Inhaled and Oral Corticosteroids)

    MedlinePlus

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

  11. Effects of exercise on dose and dose distribution of inhaled automotive pollutants. Research report, Jun 84-Oct 90

    SciTech Connect

    Kleinman, M.T.; Mautz, W.J.

    1991-01-01

    The study evaluated how changes in ventilation rate and the entry route of air pollutants into the respiratory tract (nose versus mouth breathing) affect the respiratory tract uptake and penetration of inhaled gaseous and particle pollutants in automobile emissions. Beagle dogs were exposed at rest or while exercising to nitrogen dioxide (1 and 5 ppm), formaldehyde (2 and 10 ppm), and an aerosol of ammonium nitrate particles (0.3 micro MMAD at 1 mg/m). Total respiratory system uptake and effects on breath time expired tidal volume, fractional expiration time, minute ventilation, respiratory gas exchange, ventilation equivalents for oxygen and carbon dioxide, and dynamic pulmonary resistance and compliance were measured. Regional penetration of pollutants through oral and nasal airways and pollutant uptake in the lung were measured in a separate group of six tracheostomized dogs. Dogs exposed to 5 ppm nitrogen at rest tended to breathe more rapidly and more shallowly than dogs exposed to purified air. Rapid-shallow breathing was not observed when the dogs were exposed during exercise to 5 ppm nitrogen dioxide. Dogs exposed to a mixture of 10 ppm formaldehyde and 1 mg/m 3 ammonium nitrate particles during exercise showed a shift to larger tidal volume breathing. The total respiratory system uptake of formaldehyde in the mixture was larger than that measured for 10 ppm of formaldehyde alone in another exercise and exposure study. In tracheostomized dogs exposed at rest, formaldehyde was rapidly removed from inspired air by the upper airways and penetrated to the trachea, whether breathing was by nose or mouth. Nitrogen dioxide penetrated the upper airways more readily. For both gases, penetration was greater during mouth breathing than during nose breathing, and penetration increased with increased ventilation.

  12. RECONSTRUCTING POPULATION EXPOSURES FROM DOSE BIOMARKERS: INHALATION OF TRICHLOROETHYLENE (TCE) AS A CASE STUDY

    EPA Science Inventory

    Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through bi...

  13. Inhalation dose due to presence of 131I in air above septic tank system of an endocrinology hospital.

    PubMed

    Mietelski, J W; Grabowska, S; Nowak, T; Bogacz, J; Gaca, P; Bartyzel, M; Budzanowski, M

    2005-01-01

    We present here measurements of the 131I concentration for both: gaseous and aerosol fraction of 131I in the air above the septic tank containing wastes from medical application of this isotope. Aerosols were collected using air filters, whereas gaseous forms of iodine were trapped in KI impregnated charcoal double layer cartridge. Besides an active method (pumping of the air through system of filters) an attempt for using a passive method (charcoal traps) for monitoring of radio-iodine is described. For better characterisation of a site the external kerma was determined by means of G-M and TLD techniques as well as the activity kept in the septic tank was measured by gamma spectrometry. Results show that the activity of the aerosol fraction can be neglected compared to that of the gaseous fraction. He measured activity of air is low, on the level of 1 Bq m(-3), even during simulated failure of the ventilation system. Estimated inhalation dose for the serviceman of septic tanks is low ( approximately 10%) compared with external dose obtained by such person due to gamma radiation from the tank (on the level approximately 500 nSv h(-1)). Therefore, the concept of passive monitoring of the iodine in air was abandoned. Also estimated is the efficiency of 131I reduction by a charcoal filter of the ventilation system and 131I input to the environment by the ventilation chimney. PMID:15941814

  14. DOSE PARADIGMS FOR INHALED VAPORS OF PRIMARY CARCINOGENS AND THEIR IMPACT ON RISK ASSESSMENT

    EPA Science Inventory

    In the assessment of risk, several factors affect predictions: election of reactive agent, selection of tumor incidence data, modeling of dose, scaling across species, adjustment for differences in duration and frequency of exposure, and selection of the most suitable risk extrap...

  15. HUMAN ACTIVITIES THAT MAY LEAD TO HIGH INHALED INTAKE DOSES IN CHILDREN AGED 6-13

    EPA Science Inventory

    The paper focuses on possible activities of children aged 6-13 that may make them susceptible to high hourly intake doses of ozone (O3) air pollution. Data from an O3 exposure modeling exercise indicates that a relatively few hours can account for a significant amount of the t...

  16. Respiratory dose of inhaled particulate matter and its health implications in susceptible populations.

    EPA Science Inventory

    Particulate matter (PM) in the air is known to cause adverse health effects, particularly in elderly subjects with respiratory and cardiopulmonary disease. Although observed health effects are likely caused by multiple factors, the respiratory dose is one factor of particular con...

  17. Uncertainty of inhalation dose coefficients for representative physical and chemical forms of iodine-131

    NASA Astrophysics Data System (ADS)

    Harvey, Richard Paul, III

    Releases of radioactive material have occurred at various Department of Energy (DOE) weapons facilities and facilities associated with the nuclear fuel cycle in the generation of electricity. Many different radionuclides have been released to the environment with resulting exposure of the population to these various sources of radioactivity. Radioiodine has been released from a number of these facilities and is a potential public health concern due to its physical and biological characteristics. Iodine exists as various isotopes, but our focus is on 131I due to its relatively long half-life, its prevalence in atmospheric releases and its contribution to offsite dose. The assumption of physical and chemical form is speculated to have a profound impact on the deposition of radioactive material within the respiratory tract. In the case of iodine, it has been shown that more than one type of physical and chemical form may be released to, or exist in, the environment; iodine can exist as a particle or as a gas. The gaseous species can be further segregated based on chemical form: elemental, inorganic, and organic iodides. Chemical compounds in each class are assumed to behave similarly with respect to biochemistry. Studies at Oak Ridge National Laboratories have demonstrated that 131I is released as a particulate, as well as in elemental, inorganic and organic chemical form. The internal dose estimate from 131I may be very different depending on the effect that chemical form has on fractional deposition, gas uptake, and clearance in the respiratory tract. There are many sources of uncertainty in the estimation of environmental dose including source term, airborne transport of radionuclides, and internal dosimetry. Knowledge of uncertainty in internal dosimetry is essential for estimating dose to members of the public and for determining total uncertainty in dose estimation. Important calculational steps in any lung model is regional estimation of deposition fractions

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

    PubMed

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

    2009-03-01

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

  19. Design and in vitro performance testing of multiple air classifier technology in a new disposable inhaler concept (Twincer) for high powder doses.

    PubMed

    de Boer, Anne H; Hagedoorn, Paul; Westerman, Elsbeth M; Le Brun, Paul P H; Heijerman, Harry G M; Frijlink, Henderik W

    2006-06-01

    Dry powder inhalation of antibiotics in cystic fibrosis (CF) therapy may be a valuable alternative for wet nebulisation, because it saves time and it improves lung deposition. In this study, it is shown that the use of multiple air classifier technology enables effective dispersion of large amounts of micronised powder (up to 25mg). X(50)-values of the aerosol from laser diffraction analysis obtained with the Twincer disposable inhaler concept (containing multiple air classifier technology) are practically the same as that for the pure drug in the range of dose weights between 0 and 25mg. Only for the highest dose weights, a minor fraction (5-7.5%) of small agglomerates (5-15microm) is released from the inhaler. Moreover, the size distribution of the aerosol is practically the same at 1 and 4kPa. Cascade impactor results confirm the good performance of the multiple classifier concept. Unprocessed micronised particles or soft spherical agglomerates can be used, and special particle engineering processes are not necessary. Only a minor fraction of coarse sweeper crystals in the formulation is desired to reduce the total inhaler losses for colistin sulfomethate to less than 5-6% at 4kPa. The classifiers can be designed to retain these crystals with more than 95% efficiency. PMID:16650739

  20. Tracked Active Region Patches for MDI and HMI

    NASA Astrophysics Data System (ADS)

    Turmon, Michael; Hoeksema, J. Todd; Bobra, Monica

    2014-06-01

    We describe tracked active-region patch data products that have been developed for HMI (HMI Active Region Patches, or HARPs) and for MDI (MDI Tracked Active Region Patches, or MDI TARPs). Both data products consist of tracked magnetic features on the scale of solar active regions. The now-released HARP data product covers 2010-present (>2000 regions to date). Like the HARPs, the MDI TARP data set is a catalog of active regions (ARs), indexed by a region ID number, analogous to a NOAA AR number, and time. The TARPs contain 6170 regions spanning 72000 images taken over 1996-2010, and will be availablein the MDI resident archive (RA).MDI TARPs are computed based on the 96-minute synoptic magnetograms and intensitygrams. As with the related HARP data product, the approximate threshold for significance is 100G. Use of both image types together allows faculae and sunspots to be separated out as sub-classes of activity, in addition to identifying the overall active region that they are in. After being identified in single images, the magnetically-active patches are grouped and tracked from image to image. Merges among growing active regions, as well as faint active regions hovering at the threshold of detection, are handled automatically. Regions are tracked from their inception until they decay within view, or transit off the visible disk. For each active region and for each time, a bitmap image is stored containing the precise outline of the active region. Also, metadata such as areas and integrated fluxes are stored for each AR and for each time. Because there is a cross-calibration between the HMI and MDI magnetograms (Liu et al. 2012), it is straightforward to use the same classification and tracking rules for the HMI HARPs and the MDI TARPs. We show results demonstrating region correspondence, region boundary agreement, and agreement of flux metadata using the approximately 140 regions in the May 2010-October 2010 time period. We envision several uses for these data

  1. Annual report on long-term dose-response studies of inhaled or injected radionuclides, October 1, 1989--September 30, 1990

    SciTech Connect

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L. . Inhalation Toxicology Research Inst.)

    1991-03-01

    This report, is divided into two main sections dealing with the Inhalation Toxicology Research Institute (ITRI) and Utah studies. These sections are organized along similar lines, addressing basic research approaches, study designs, recent accomplishments and the current status of study-completion activities. Study-specific features are presented for the 19 major studies being conducted with either inhaled beta- or alpha-emitting radionuclides. A broad range of dose- and effect-modifying factors are being examined including the effects of total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and exposure mode. The ITRI section of this report concludes with a group of brief reports of recent accomplishments. These accomplishments fall into five general categories: dosimetry, dose-response results for beta-emitting radionuclides, dose-response results for alpha-emitting radionuclides, molecular mechanism of carcinogenesis, and immunologic studies of exposed and aging dogs. The other major section this annual report describes the current status and recent progress of the life-span studies from the University of Utah. The main difference between the Utah studies and the ITRI studies is the exposure route. All of the Utah studies involved exposure by intravenous injection whereas all the ITRI exposures, except for {sup 137}CsCl, were given by single or repeated inhalation exposures. The research efforts currently devoted to the Utah studies fall into three main areas: continuation of the care and study of dogs still alive in these studies, detailed dosimetric studies, at the organ and local levels, of injected radionuclides and the factors that influence dose patterns, and completion of final reviews of biological materials and data, compilations and analyses of data, and preparation of final study reports for publication in the open, scientific literature.

  2. Developmental toxicity of inhaled methanol in the CD-1 mouse, with quantitative dose-response modeling for estimation of benchmark doses

    SciTech Connect

    Rogers, J.M.; Mole, M.L.; Chernoff, N.; Barbee, B.D.; Turner, C.I.

    1993-01-01

    Pregnant CD-1 mice were exposed to 1,000, 2,000, 5,000, 7,500, 10,000, or 15,000 ppm on methanol for 7 hr/day on days 6-15 of gestation. On day 17 of gestation, remaining mice were weighed, killed and the gravid uterus was removed. Numbers of implantation sites, live and dead fetuses and resorptions were counted, and fetuses were examined externally and weighed as a litter. Significant increases in the incidence of exencephaly and cleft palate were observed at 5,000 ppm and above, increased postimplantation mortality at 7,500 ppm and above (including an increasing incidence of full-litter resorption), and reduced fetal weight at 10,000 ppm and above. A dose-related increase in cervical ribs or ossification sites lateral to the seventh cervical vertebra was significant at 2,000 ppm and above. Thus, the NOAEL for the developmental toxicity in this study is 1,000 ppm. The results of this study indicate that inhaled methanol is developmentally toxic in the mouse at exposure levels which were not maternally toxic. Litters of pregnant mice gavaged orally with 4 g methanol/kg displayed developmental toxic effects similar to those seen in the 10,000 ppm methanol exposure group. (Copyright (c) 1993 Wiley-Liss, Inc.)

  3. Differences in physical chemistry and dissolution rate of solid particle aerosols from solution pressurised inhalers.

    PubMed

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

    2014-04-25

    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. PMID:24491530

  4. Umeclidinium Oral Inhalation

    MedlinePlus

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

  5. Poly(amidoamine) Dendrimer-Doxorubicin Conjugates: In Vitro Characteristics and Pseudosolution Formulation in Pressurized Metered-Dose Inhalers.

    PubMed

    Zhong, Qian; da Rocha, Sandro R P

    2016-03-01

    Lung cancers are the leading cause of cancer death for both men and women. A series of PEGylated poly(amidoamine) dendrimer-based doxorubicin (DOX) nanocarriers (G3NH2-mPEG-nDOX) were synthesized and their chemistry tailored for the development of novel pseudosolution formulations in propellant-based metered-dose inhalers (pMDIs) with enhanced aerosol characteristics. A pH-labile bond was used to conjugate DOX to dendrimer for controlled intracellular release. We employed a two-step PEGylation strategy to cover a range of DOX loading and PEGylation density. We investigated the impact of pH, PEGylation density, and DOX payload on the release of DOX from the conjugate. We also determined the cellular internalization of the conjugate, the intracellular release kinetics of DOX from the conjugate, and their ability to kill human alveolar carcinoma cells (A549). The acid-labile conjugates sustained the release of DOX in acidic medium, and also intracellularly, as determined by nuclear colocalization studies with confocal microscopy. Meanwhile, DOX was retained in the conjugate at extracellular physiological conditions, indicating their potential to achieve spatial and temporal controlled release profiles. We also observed that the kinetics of cellular entry of the conjugates with DOX increased significantly compared to free DOX. Due to controlled release, the G3NH2-mPEG-nDOX conjugates showed time-dependent cell kill, but their cell kill ability was comparable to free DOX, which suggests their potential in vivo as compared to free DOX. The conjugates were formulated in pMDIs as pseudosolution formulations, with the help of a minimum amount of cosolvent (ethanol; <0.4%; v/v). The physical stability and aerosol characteristics of the conjugates were controlled by the PEGylation density of the carriers: the higher the PEG density, the better the dispersibility and the better the deep lung deposition of the conjugates (fine particle fraction up to ca. 80%). PMID:26832992

  6. Effect of Device Design and Formulation on the In Vitro Comparability for Multi-Unit Dose Dry Powder Inhalers.

    PubMed

    Shur, Jagdeep; Saluja, Bhawana; Lee, Sau; Tibbatts, James; Price, Robert

    2015-09-01

    The focus of this investigation was to understand the design space to achieve comparable in vitro performance of two multi-unit dose dry powder inhalers (DPIs)—Flixotide® Accuhaler® (reference product) and MultiHaler® (test product). Flow field, pressure drop and particle trajectories within the test and reference DPI devices were modelled via computational fluid dynamics (CFD). Micronized fluticasone propionate (FP) was characterized to determine particle size distribution (PSD), specific surface area (SSA) and surface interfacial properties using cohesive-adhesive balance (CAB). CFD simulations suggested that the pressure drop and airflow velocity in the MultiHaler® were greater than Accuhaler®. Two modified test devices (MOD MH 1 and MOD MH 2) were manufactured with the introduction of by-pass channels in the airflow path, which achieved comparable specific resistance and airflow path between the test and reference devices. Assessment of reference product formulation in modified test devices suggested that MOD MH 2 achieved comparable in vitro performance to the reference product. CAB analysis suggested that adhesion of all FP batches to lactose was different, with batch D showing greatest and batch A least adhesion to lactose. Test DPI formulations were manufactured using four different batches of FP with milled or sieved lactose, and showed that batch A FP formulated with sieved lactose in MOD MH 2 device demonstrated the highest degree of similarity to the Accuhaler® in vitro deposition. Application of CFD modelling and material characterization of formulation raw materials enabled the modification of device and formulation critical material attributes to create an in vitro comparable device/formulation system to the reference product. PMID:25956383

  7. Effect of high dose inhaled glucocorticoids on quality of life in patients with moderate to severe asthma.

    PubMed

    Choi, Jae-Sung; Jang, An-Soo; Lee, June-Hyuk; Park, Jong-Sook; Park, Sung-Woo; Kim, Do-Jin; Park, Choon-Sik

    2005-08-01

    Asthma is a chronic disorder that can place considerable restrictions on the physical, emotional, and social aspects of the lives of patients. Inhaled glucocorticoids (GCs) are the most effective controller therapy. The purpose of this study was to evaluate the effect of inhaled GCs on quality of life in patients with moderate to severe asthma. Patients completed the asthma quality of life questionnaire (AQLQ) and pulmonary function test at baseline and after 4 wks treatment of GCs. We enrolled 60 patients who had reversibility in FEV1 after 200 microgram of albuterol of 15% or more and/or positive methacholine provocation test, and initial FEV1% predicted less than 80%. All patients received inhaled GCs (fluticasone propionate 1,000 microgram/day) for 4 wks. The score of AQLQ was significantly improved following inhaled GCs (overall 51.9+/-14.3 vs. 67.5+/-12.1, p<0.05). The change from day 1 to day 28 in FEV1 following inhaled GCs was diversely ranged from -21.0% to 126.8%. The improvement of score of AQLQ was not different between at baseline and after treatment of GCs according to asthma severity and GCs responsiveness. Quality of life was improved after inhaled GCs regardless of asthma severity and GCs responsiveness in patients with moderate to severe asthma. PMID:16100448

  8. Health Literacy, Cognitive Function, Proper Use, and Adherence to Inhaled Asthma Controller Medications Among Older Adults With Asthma

    PubMed Central

    Wolf, Michael S.; Smith, Samuel G.; Martynenko, Melissa; Vicencio, Daniel P.; Sano, Mary; Wisnivesky, Juan P.; Federman, Alex D.

    2015-01-01

    BACKGROUND: We sought to investigate the degree to which cognitive skills explain associations between health literacy and asthma-related medication use among older adults with asthma. METHODS: Patients aged ≥ 60 years receiving care at eight outpatient clinics (primary care, geriatrics, pulmonology, allergy, and immunology) in New York, New York, and Chicago, Illinois, were recruited to participate in structured, in-person interviews as part of the Asthma Beliefs and Literacy in the Elderly (ABLE) study (n = 425). Behaviors related to medication use were investigated, including adherence to prescribed regimens, metered-dose inhaler (MDI) technique, and dry powder inhaler (DPI) technique. Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Cognitive function was assessed in terms of fluid (working memory, processing speed, executive function) and crystallized (verbal) ability. RESULTS: The mean age of participants was 68 years; 40% were Hispanic and 30% non-Hispanic black. More than one-third (38%) were adherent to their controller medication, 53% demonstrated proper DPI technique, and 38% demonstrated correct MDI technique. In multivariable analyses, limited literacy was associated with poorer adherence to controller medication (OR, 2.3; 95% CI, 1.29-4.08) and incorrect DPI (OR, 3.51; 95% CI, 1.81-6.83) and MDI (OR, 1.64; 95% CI, 1.01-2.65) techniques. Fluid and crystallized abilities were independently associated with medication behaviors. However, when fluid abilities were added to the model, literacy associations were reduced. CONCLUSIONS: Among older patients with asthma, interventions to promote proper medication use should simplify tasks and patient roles to overcome cognitive load and suboptimal performance in self-care. PMID:25275432

  9. Fluticasone and Salmeterol Oral Inhalation

    MedlinePlus

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

  10. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: effects of epinephrine and oxygen therapies.

    PubMed

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G; Xu, Fadi; Russell, Robert G; Sopori, Mohan L

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD50 sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD50 sarin-exposed animals were administered the bronchodilator epinephrine, >90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD50 sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. PMID:24269878

  11. The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers.

    PubMed

    Smyth, Hugh D C; Beck, Vance P; Williams, Dennis; Hickey, Anthony J

    2004-02-10

    The purpose of this study was to evaluate the hypothesis that spacer devices have limited effect on the in vitro fine particle dose emitted from solution metered dose inhalers containing different proportions of HFA134a [1,1,1,2,-tetrafluoroethane] propellant. Two solution formulations (80% and 97.5% wt/wt HFA134a) were tested across the actuator alone, actuator plus Aerochamber, and Ace holding chamber. Particle size distributions were determined using laser diffraction (LD) and cascade impaction (CI). Multimodal particle size distributions were identified using LD. CI analyses were characterized by a major mode located at approximately 0.5 microm. The fine particle dose emitted from the inhaler spacer combinations containing 97.5% HFA134a was independent of the device setup used. Fine particle doses were influenced by spacer setup in 80% HFA134a formulations, indicating different plume dynamics of low vapor pressure formulations. Sampling inlet deposition was approximately 0 when spacer devices were used with either formulation. When spacers were not used, sampling inlet deposition was increased significantly. However, inlet deposition with the 97.5% HFA134a formulation was significantly less than that of the 80% HFA134a formulation (approximately 25% of emitted dose compared with 69%, respectively). Thus, high propellant concentration formulations appear to have more robust in vitro performance. This is particularly important given the preponderance of poor patient compliance that is associated with spacer use. High propellant concentrations had the advantage of fine particle doses that were independent of the device setup and significantly lowered sampling inlet deposition when no spacer was used. PMID:15198528

  12. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

    SciTech Connect

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.; Xu, Fadi; Russell, Robert G.; Sopori, Mohan L.

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD{sub 50} sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily.

  13. Immunochemical detection of the occupational allergen, methylene diphenyl diisocyanate (MDI), in situ.

    PubMed

    Wisnewski, Adam V; Liu, Jian

    2016-02-01

    Diisocyanate chemicals essential to polyurethane production are a well-recognized cause of occupational asthma. The pathogenesis of diisocyanate-induced asthma, including the pathways by which the chemical is taken up and its distribution in exposed tissue, especially the lung, remains unclear. We developed an antiserum with specificity for methylene diphenyl diisocyanate (MDI) the most abundantly produced and utilized diisocyanate world-wide, and established its ability to detect MDI in situ. Polyclonal MDI-specific IgG was induced by immunizing rabbits with MDI-conjugated to keyhole limpet hemocyanin (KLH) emulsified in complete Freund's adjuvant, followed by two booster injections with incomplete Freund's adjuvant. The antiserum contains IgG that recognize a variety of different MDI conjugated proteins, but not unconjugated or mock exposed proteins by dot blot analysis. The antiserum further demonstrates specificity for proteins conjugated with MDI, but not other commonly used diisocyanates. Immunochemical studies with cytospun airway cells and formalin-fixed paraffin embedded lung tissue sections from mice intranasally exposed to MDI (as reversibly reactive glutathione conjugates, e.g. GSH-MDI) demonstrated the antiserum's ability to detect MDI in tissue samples. The data demonstrate penetration of MDI into the lower airways, localized deposition in the epithelial region surrounding airways, and uptake by alveolar macrophages. The new immunochemical reagent should be useful for further studies delineating the uptake and tissue distribution of MDI, especially as it relates to adverse health effects from exposure. PMID:26690039

  14. Assessing the reliability of dose coefficients for ingestion and inhalation of 226Ra and 90Sr by members of the public.

    PubMed

    Puncher, M

    2014-01-01

    Assessments of risk to a population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficient, E(50), used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the risk is important for informing judgements on reliability. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioisotopes of the alkaline earth metals, (90)Sr and (226)Ra, by members of the UK public. The study derives uncertainties in biokinetic model parameter values to calculate the distributions of the effective dose per unit intake using the ICRP Publication 60 formalism. The distributions are used to infer the uncertainty on the mean effective dose per unit intake to inform the derivation of uncertainty factors (UF) for the appropriate ICRP Publication 72 dose coefficients. Here, a UF indicates a 95 % probability that the best estimate of risk per unit intake is within a factor, UF, of the nominal risk associated with the appropriate ICRP dose coefficient, E(50), with respect to uncertainties in the biokinetic model parameter values. Ingestion: it is assumed that exposure occurs through the ingestion of radionuclides present in food and water. The results for both radionuclides suggest a UF of within 3 for all age groups, with median values close to the ICRP values. Inhalation: it is assumed that environmental exposure to radium occurs primarily due to insoluble forms present in fly ash discharged from coal-fired power stations; for strontium, exposure is assumed to occur due to residual aerosols produced as a result of atmospheric nuclear testing and nuclear reactor accidents. The results suggest a UF of around 3 and 6 for inhalation of (90)Sr and (226)Ra, respectively, by members of the public. PMID:23896416

  15. An Emerging Magnetic Flux Catalog for SOHO/MDI

    NASA Astrophysics Data System (ADS)

    Lamb, Derek; Munoz-Jaramillo, Andres; DeForest, Craig

    2016-05-01

    We present a catalog of emerging magnetic flux events covering the entirety of the 15-year-long SOHO/MDI 96-minute magnetogram dataset. Such a catalog has myriad uses in studies of the solar dynamo and solar cycle. Our catalog is designed to mimic as nearly as possible the Emerging Flux region catalog produced for SDO/HMI, allowing continuity across missions and solar cycles. We will present details of the algorithm for identifying emerging flux events, special considerations for MDI as opposed to HMI, detailed examples of some detected emerging flux regions, and a brief overview of statistics of the entire catalog. The catalog will be available for querying through the Heliophysics Event Knowledgebase, as well as for direct downloading from Southwest Research Institute. This work has been supported by NASA Grant NNX14AJ67G through the Heliophysics Data Environment Enhancements program.

  16. The nature of the MDI/wood bond

    SciTech Connect

    Marcinko, J.J.; Phanopoulos, C.; Newman, W.H.

    1995-12-01

    Polymeric diphenylmethane diisocyanate (pMDI) binders have been used in the wood composite industry for 20 years. Almost one half of the oriented strand board (OSB) manufactures in North America are taking advantage of its processing speed and superior board performance. MDI`s current use in Strandboard, MDF (medium density fiber board), LVL (laminated veneer lumber), Plywood, and Particleboard is wide spread. A fundamental understanding of the role of MIDI as a binder in these complex composites is essential for further processing optimization. Experimental data is presented which investigates the nature of the chemical bonding in wood composites. Solid state nuclear magnetic resonance (NMR) data is combined with data from thermal analysis and fluorescence microscopy to investigate the chemistry, penetration, and morphology of the isocyanate/wood interphase. Structure property relationships are developed and related to composite performance. The study contrasts isocyanate and phenol formaldehyde binder systems.

  17. In Vitro Determination of Respimat® Dose Delivery in Children: An Evaluation Based on Inhalation Flow Profiles and Mouth–Throat Models

    PubMed Central

    Bickmann, Deborah; Kamin, Wolfgang; Sharma, Ashish; Moroni-Zentgraf, Petra; Zielen, Stefan

    2016-01-01

    Abstract Background: Aerosol therapy in young children can be difficult. A realistic model based on handling studies and in vitro investigations can complement clinical deposition studies and be used to enable dose-to-the-lung (DTL) predictions. Methods: Predictions on dose delivery to the lung were based on (1) representative inhalation flow profiles from children enrolled in a Respimat® handling study, (2) in vitro measurement of the fine-particle DTL using mouth–throat models derived from nuclear magnetic resonance/computed tomography (NMR/CT) scans of children, and (3) a mathematical model to predict the tiotropium DTL. Accuracy of the prediction was confirmed using pharmacokinetic (PK) data from children with cystic fibrosis enrolled in a phase 3 clinical trial of tiotropium Respimat with valved holding chamber (VHC). Results: Representative inhalation flow profiles for each age group were obtained from 56 children who successfully inhaled a volume >0.15 L from the Respimat with VHC. Average dimensions of the mouth–throat region for 38 children aged 1–<2 years, 2–<3 years, 3–<4 years, and 4–<5 years were determined from NMR/CT scans. The DTL from the Respimat plus VHC were determined by in vitro measurement and were 5.1±1.1%, 15.6%±1.4%, 17.9%±1.5%, and 37.1%±1.8% of the delivered dose for child models 0–<2 years, 2–<3 years, 3–<4 years, and 4–<5 years, respectively. This provides a possible explanation for the age dependence of clinical PK data obtained from the phase 3 tiotropium trial. Calculated in vitro DTL per body mass (μg/kg [±SD]) were 0.031±0.014, 0.066±0.031, 0.058±0.024, and 0.059±0.029, respectively, compared to 0.046 in adults. Therefore, efficacy of the treatment was not negatively impacted in spite of the seemingly low percentages of the DTL. Conclusions: We conclude that the combination of real-life inhalation profiles with respective mouth–throat models and in vitro determination of delivered DTL is a good

  18. Application of USP inlet extensions to the TSI impactor system 3306/3320 using HFA 227 based solution metered dose inhalers.

    PubMed

    Mogalian, Erik; Myrdal, Paul Brian

    2005-12-01

    The objective of this study was to further evaluate the need for a vertical inlet extension when testing solution metered dose inhalers using the TSI Model 3306 Impactor Inlet in conjunction with the TSI Model 3320 Aerodynamic Particle Sizer (APS). The configurations tested using the TSI system were compared to baseline measurements that were performed using the Andersen Mark II 8-stage cascade impactor (ACI). Seven pressurized solution metered dose inhalers were tested using varied concentrations of beclomethasone dipropionate (BDP), ethanol, and HFA 227 propellant. The inhalers were tested with the cascade impactor, and with the TSI system. The TSI system had three different configurations as the manufacturer provided (0 cm) or with inlet extensions of 20 and 40 cm. The extensions were located between the USP inlet and the Model 3306 Impactor Inlet. There were no practical differences between each system for the stem, actuator, or USP inlet. The fine particle mass (aerodynamic mass < 4.7 microm) was affected by extension length and correlated well with the ACI when an extension was present. APS particle size measurements were unaffected by the extension lengths and correlated well to particle size determined from the ACI analysis. It has been confirmed that an inlet extension may be necessary for the TSI system in order to give mass results that correlate to the ACI, especially for formulations having significant concentrations of low volatility excipients. Additionally, the results generated from this study were used to evaluate the product performance of HFA 227 based solution formulations that contain varying concentrations of ethanol as a cosolvent. PMID:16316853

  19. Inhalation Injuries

    MedlinePlus

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

  20. Combined fluticasone furoate/vilanterol reduces decline in lung function following inhaled allergen 23 h after dosing in adult asthma: a randomised, controlled trial

    PubMed Central

    2012-01-01

    Background There is a need for preventative asthma maintenance therapy that provides lasting bronchoprotection against allergen provocation. Fluticasone furoate (FF) is a novel inhaled once-daily corticosteroid, being investigated as monotherapy for asthma and in combination with vilanterol (VI), a novel inhaled once-daily long-acting beta-agonist, for asthma and chronic obstructive pulmonary disease. Methods In a crossover study of 52 subjects with mild asthma, FF/VI 100/25mcg and FF 100 dosed once-daily in the evening for 28 days were compared with placebo to evaluate their capacity to provide bronchoprotection against the early asthmatic response (EAR) stimulated by an inhaled allergen challenge. Bronchoprotection was assessed by change from post-saline baseline in weighted mean (wm) forced expiratory volume in 1 s (FEV1) for the first 2 h post-allergen challenge, which was on Day 29 (22–23 h post final dose on Day 28). The EAR was also assessed using maximum percent decrease from post-saline baseline and minimum absolute FEV1; the incidence of adverse events was a secondary endpoint. Results FF/VI 100/25 and FF 100 both provided significant bronchoprotection against the EAR for all endpoints assessed. For wmFEV1 over the first 2 h post-allergen challenge, a 162 mL (95% CI, 87 to 237 mL) difference was observed between placebo and FF 100, while a 145 mL (95% CI, 69 to 222 mL) difference was observed between placebo and FF/VI 100/25 treatment. No difference between active treatments was observed (−17 mL; 95% CI, –91 to 57 mL). Both treatments were well tolerated. Conclusions FF 100 alone and in combination with VI 25 provides significant bronchoprotection against the EAR in subjects with mild asthma. That this protection is provided at the trough of dosing, i.e. 23 h post last dose, supports the utility of FF 100 and FF/VI 100/25 as viable once-daily therapies. Trial registration Clinicaltrials.gov identifier: NCT01128569, GSK Study

  1. Fluticasone Oral Inhalation

    MedlinePlus

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

  2. Overview of inhalation toxicology.

    PubMed Central

    Dorato, M A

    1990-01-01

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

  3. Limiting values of radionuclide intake and air concentration and dose conversion factors for inhalation, submersion, and ingestion: Federal guidance report No. 11

    SciTech Connect

    Eckerman, K.F.; Wolbarst, A.B.; Richardson, A.C.B.

    1988-09-01

    Radiation protection programs for workers are based, in the United States, on a hierarchy of limitations stemming from Federal guidance approved by the President. This guidance, which consists of principles, policies, and numerical primary guides, is used by Federal agencies as the basis for developing and implementing their own regulatory standards. The primary guides are usually expressed in terms of limiting doses to workers. The protection of workers against taking radioactive materials into the body, however, is accomplished largely through the use of regulations based on derived guides expressed in terms of quantities or concentrations of radionuclides. The values of these derived guides are chosen so as to assure that workers in work environments that conform to them are unlikely to receive radiation doses that exceed the primary guides. The purpose of the present report is to set forth derived guides that are consistent with current Federal radiation protection guidance. They are intended to serve as the basis for regulations setting upper bounds on the inhalation and ingestion of, and submersion in, radioactive materials in the workplace. The report also includes tables of exposure-to-dose conversion factors, for general use in assessing average individual committed doses in any population that is adequately characterized by Reference Man. 38 refs.

  4. TARPs: Tracked Active Region Patches from SoHO/MDI

    NASA Astrophysics Data System (ADS)

    Turmon, M.; Hoeksema, J. T.; Bobra, M.

    2013-12-01

    We describe progress toward creating a retrospective MDI data product consisting of tracked magnetic features on the scale of solar active regions, abbreviated TARPs (Tracked Active Region Patches). The TARPs are being developed as a backward-looking extension (covering approximately 3500 regions spanning 1996-2010) to the HARP (HMI Active Region Patch) data product that has already been released for HMI (2010-present). Like the HARPs, the MDI TARP data set is designed to be a catalog of active regions (ARs), indexed by a region ID number, analogous to a NOAA AR number, and time. TARPs from MDI are computed based on the 96-minute synoptic magnetograms and pseudo-continuum intensitygrams. As with the related HARP data product, the approximate threshold for significance is 100G. Use of both image types together allows faculae and sunspots to be separated out as sub-classes of activity, in addition to identifying the overall active region that the faculae/sunspots are part of. After being identified in single images, the magnetically-active patches are grouped and tracked from image to image. Merges among growing active regions, as well as faint active regions hovering at the threshold of detection, are handled automatically. Regions are tracked from their inception until they decay within view, or transit off the visible disk. The final data product is indexed by a nominal AR number and time. For each active region and for each time, a bitmap image is stored containing the precise outline of the active region. Additionaly, metadata such as areas and integrated fluxes are stored for each AR and for each time. Because there is a calibration between the HMI and MDI magnetograms (Liu, Hoeksema et al. 2012), it is straightforward to use the same classification and tracking rules for the HARPs (from HMI) and the MDI TARPs. We anticipate that this will allow a consistent catalog spanning both instruments. We envision several uses for the TARP data product, which will be

  5. Annual report on long-term dose-response studies of inhaled or injected radionuclides, October 1, 1988--September 30, 1989

    SciTech Connect

    Boecker, B.B.; Muggenburg, B.A. . Inhalation Toxicology Research Inst.); Miller, S.C.; Coons, T.A. . Radiobiology Div.)

    1990-08-01

    Since 1967, it has been customary for the staff of the Inhalation Toxicology Research Institute (ITRI) to publish an annual report presenting highlights of the past year's research accomplishments. In each annual report up to the present year, a substantial amount of information was presented on the status of the life-span studies of dogs that inhaled different alpha- or beta-emitting radionuclides. This information was presented as topical research reports, status reports on each study and appendices containing dose and response data for individual dogs in each study. Collectively, these reports provide a valuable history of each study and the general observations that have been made to date. When plans were made for the 1988--1989 ITRI Annual Report, it was decided to publish all information on these life-span studies in a separate periodic report. This report, which is the first to deal with these lifespan studies separately, is designed to have stand-alone informational content regarding current data and also to provide references to past annual reports. It is anticipated that this report will be published annually and maintain the flow of study-related information that has been a hallmark of previous ITRI Annual Reports. This report presents detailed information on both the ITRI and University of Utah radionuclide toxicity studies of dogs. The incorporation of annual information on the Utah-initiated studies reflects the current ITRI/Utah relationship established by DOE/OHER for completion of these studies. 53 figs., 47 tabs.

  6. Rats with Chronic, Stable Pulmonary Hypertension Tolerate Low Dose Sevoflurane Inhalation as Well as Normal Rats Do

    PubMed Central

    Qin, Gang; Luo, Hui; Liu, Xiao; Zhang, Fan; Ye, Zhi; Zhang, Junjie; Wang, E.

    2016-01-01

    Background The effects of low concentration of sevoflurane on right ventricular (RV) function and intracellular calcium in the setting of pulmonary arterial hypertension (PAH) have not been investigated clearly. We aim to study these effects and associated signaling pathways in rats with PAH. Methods Hemodynamics were assessed with or without sevoflurane inhalation in established PAH rats. We analysis the classic RV function parameters and RV-PA coupling efficiency using steady-state PV loop recordings. The protein levels of SERCA2, PLB and p-PLB expression was analyzed by western blot to assess their relevance in PAH. Results Rats with PAH presented with RV hypertrophy and increased pulmonary arterial pressure. The values of Ea, R/L ratio, ESP, SW, PRSW, +dP/dtmax and the slope of the dP/dtmax-EDV relationship increased significantly in PAH rats (P<0.05). Sevoflurane induced a concentration-dependent decrease of systemic and pulmonary blood pressure, HR, RV contractility, and increased the R/L ratio in both groups. Sevoflurane reduced the expression of SERCA2 and increased the expression of PLB in both groups. Interestingly, sevoflurane only reduced the p-PLB/PLB ratio in PAH rats, not in normal rats. Conclusions Rats with chronic, stable pulmonary hypertension tolerate low concentrations of sevoflurane inhalation as well as normal rats do. It may be related to the modulation of the SERCA2-PLB signaling pathway. PMID:27144451

  7. SOI/MDI studies of active region seismology and evolution

    NASA Technical Reports Server (NTRS)

    Tarbell, Ted D.; Title, Alan; Hoeksema, J. Todd; Scherrer, Phil; Zweibel, Ellen

    1995-01-01

    The solar oscillations investigation (SOI) will study solar active regions using both helioseismic and conventional observation techniques. The Michelson Doppler imager (MDI) can perform Doppler continuum and line depth imagery and can produce longitudinal magnetograms, showing either the full disk or a high resolution field of view. A dynamics program of continuous full disk Doppler observations for two months per year, campaign programs of eight hours of continuous observation per day, and a synoptic magnetic program of about 15 full disk magnetograms per day, are planned. The scientific plans, measurements and observation programs, are described.

  8. Assessing the impact of the duration and intensity of inhalation exposure on the magnitude of the variability of internal dose metrics in children and adults.

    PubMed

    Valcke, Mathieu; Krishnan, Kannan

    2011-12-01

    The objective of this study was to assess the impact of the exposure duration and intensity on the human kinetic adjustment factor (HKAF). A physiologically based pharmacokinetic model was used to compute target dose metrics (i.e. maximum blood concentration (C(max)) and amount metabolized/L liver/24  h (Amet)) in adults, neonates (0-30 days), toddlers (1-3 years), and pregnant women following inhalation exposure to benzene, styrene, 1,1,1-trichloroethane and 1,4-dioxane. Exposure scenarios simulated involved various concentrations based on the chemical's reference concentration (low) and six of U.S. EPA's Acute Exposure Guideline Levels (AEGLs) (high), for durations of 10  min, 60  min, 8  h, and 24  h, as well as at steady-state. Distributions for body weight (BW), height (H), and hepatic CYP2E1 content were obtained from the literature or from P3M software, whereas blood flows and tissue volumes were calculated from BW and H. The HKAF was computed based on distributions of dose metrics obtained by Monte Carlo simulations [95th percentile in each subpopulation/median in adults]. At low levels of exposure, ranges of C(max)-based HKAF were 1-6.8 depending on the chemical, with 1,4-dioxane exhibiting the greatest values. At high levels of exposure, this range was 1.1-5.2, with styrene exhibiting the greatest value. Neonates were always the most sensitive subpopulation based on C(max), and pregnant women were most sensitive based on Amet in the majority of the cases (1.3-2.1). These results have shown that the chemical-specific HKAF varies as a function of exposure duration and intensity of inhalation exposures, and sometimes exceeds the default value used in risk assessments. PMID:22084919

  9. Time-Distance Helioseismology with the MDI Instrument: Initial Results

    NASA Technical Reports Server (NTRS)

    Duvall, T. L., Jr.; Kosovichev, A. G.; Scherrer, P. H.; Bogart, R. S.; Bush, R. I.; DeForest, C.; Hoeksema, J. T.; Schou, J.; Saba, J. L. R.; Tarbell, T. D.; Title, A. M.; Wolfson, C. J.; Milford, P. N.

    1997-01-01

    In time-distance helioseismology, the travel time of acoustic waves is measured between various points on the solar surface. To some approximation, the waves can be considered to follow ray paths that depend only on a mean solar model, with the curvature of the ray paths being caused by the increasing sound speed with depth below the surface. The travel time is effected by various inhomogeneities along the ray path, including flows, temperature inhomogeneities, and magnetic fields. By measuring a large number of times between different locations and using an inversion method, it is possible to construct 3-dimensional maps of the subsurface inhomogeneities. The SOI/MDI experiment on SOHO has several unique capabilities for time-distance helioseismology. The great stability of the images observed without benefit of an intervening atmosphere is quite striking. It his made it possible for us to detect the travel time fo separations of points as small as 2.4 Mm in the high-resolution mode of MDI (0.6 arc sec 1/pixel). This has enabled the detection of the supergranulation flow. Coupled with the inversion technique, we can now study the 3-dimensional evolution of the flows near the solar surface.

  10. A FIM Study to Assess Safety and Exposure of Inhaled Single Doses of AP301—A Specific ENaC Channel Activator for the Treatment of Acute Lung Injury

    PubMed Central

    Schwameis, Richard; Eder, Sandra; Pietschmann, Helmut; Fischer, Bernhard; Mascher, Hermann; Tzotzos, Susan; Fischer, Hendrik; Lucas, Rudolf; Zeitlinger, Markus; Hermann, Robert

    2014-01-01

    AP301 is an activator of ENaC-mediated Na+ uptake for the treatment of pulmonary permeability edema in acute respiratory distress syndrome (ARDS). The purpose of this “first-in-man” study was to examine local and systemic safety and systemic exposure of ascending single doses of AP301, when inhaled by healthy male subjects. In a double-blind, placebo-controlled study, 48 healthy male subjects were randomized to 6 ascending dose groups (single doses up to 120 mg) of 8 subjects each (3:1 randomization of AP301: placebo). Serial assessments included spirometry, exhaled nitric oxide (eNO), vital signs, ECG, safety laboratory, adverse events (AE), and blood samples for the quantification of AP301 in plasma. Descriptive statistics was applied. All 48 subjects received treatment, and completed the study as per protocol. No serious, local (e.g., hoarseness, cough, bronchospasm), or dose-limiting AEs were noted. None of the assessments indicated notable dose or time-related alterations of safety outcomes. Observed AP301 systemic exposure levels were very low, with mean Cmax values of <2.5 ng/mL in the highest dose groups. Inhaled AP301 single doses up to 120 mg were safe and well tolerated by healthy male subjects. Distribution of inhaled AP301 was largely confined to the lung, as indicated by very low AP301 systemic exposure levels. PMID:24515273

  11. Fluticasone and Vilanterol Oral Inhalation

    MedlinePlus

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

  12. Umeclidinium and Vilanterol Oral Inhalation

    MedlinePlus

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

  13. Chronic cigarette smoke exposure increases the pulmonary retention and radiation dose of {sup 239}Pu inhaled as {sup 239}PuO{sub 2} by F344 rats

    SciTech Connect

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

    1998-12-01

    As a portion of a study to examine how chronic cigarette smoke exposure might alter the risk of lung tumors from inhaled {sup 239}PuO{sub 2} in rats, the effects of smoke exposure on alpha-particle lung dosimetry over the life-span of exposed rats were determined. Male and female rats were exposed to inhaled {sup 239}PuO{sub 2} alone or in combination with cigarette smoke. Animals exposed to filtered air along served as controls for the smoke exposure. Whole-body exposure to mainstream smoke diluted to concentrations of either 100 or 250 mg total particulate matter m{sup {minus}3} began at 6 wk of age and continued for 6 h d{sup {minus}1}, 5 d wk{sup {minus}1}, for 30 mo. A single, pernasal, acute exposure to {sup 239}PuO{sub 2} was given to all rats at 12 wk of age. Exposure to cigarette smoke caused decreased body weight gains in a concentration dependent manner. Lung-to-body weight ratios were increased in smoke-exposed rats. Rats exposed to cigarette smoke before the {sup 239}PuO{sub 2} exposure deposited less {sup 239}Pu in the lung than did controls. Except for male rats exposed to LCS, exposure to smoke retarded the clearance of {sup 239}Pu from the lung compared to control rats through study termination at 870 d after {sup 239}PuO{sub 2} exposure. Radiation doses to lungs were calculated by sex and by exposure group for rats on study for at least 360 d using modeled body weight changes, lung-to-body weight ratios, and standard dosimetric calculations. For both sexes, estimated lifetime radiation doses from the time of {sup 239}PuO{sub 2} exposure to death were 3.8 Gy, 4.4 Gy, or 6.7 Gy for the control, LCS, or HCS exposure groups, respectively. Assuming an approximately linear dose-response relationship between radiation dose and lung neoplasm incidence, approximate increases of 20% or 80% in tumor incidence over controls would be expected in rats exposed to {sup 239}PuO{sub 2} and LCS or {sup 239}PuO{sub 2} and HCS, respectively.

  14. Inhalant Abuse

    MedlinePlus

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

  15. Mometasone Oral Inhalation

    MedlinePlus

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

  16. Tiotropium Oral Inhalation

    MedlinePlus

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

  17. Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset.

    PubMed

    Conolly, Rory B; Kimbell, Julia S; Janszen, Derek; Schlosser, Paul M; Kalisak, Darin; Preston, Julian; Miller, Frederick J

    2004-11-01

    Formaldehyde inhalation at 6 ppm and above causes nasal squamous cell carcinoma (SCC) in F344 rats. The quantitative implications of the rat tumors for human cancer risk are of interest, since epidemiological studies have provided only equivocal evidence that formaldehyde is a human carcinogen. Conolly et al. (Toxicol. Sci. 75, 432-447, 2003) analyzed the rat tumor dose-response assuming that both DNA-reactive and cytotoxic effects of formaldehyde contribute to SCC development. The key elements of their approach were: (1) use of a three-dimensional computer reconstruction of the rat nasal passages and computational fluid dynamics (CFD) modeling to predict regional dosimetry of formaldehyde; (2) association of the flux of formaldehyde into the nasal mucosa, as predicted by the CFD model, with formation of DNA-protein cross-links (DPX) and with cytolethality/regenerative cellular proliferation (CRCP); and (3) use of a two-stage clonal growth model to link DPX and CRCP with tumor formation. With this structure, the prediction of the tumor dose response was extremely sensitive to cell kinetics. The raw dose-response data for CRCP are J-shaped, and use of these data led to a predicted J-shaped dose response for tumors, notwithstanding a concurrent low-dose-linear, directly mutagenic effect of formaldehyde mediated by DPX. In the present work the modeling approach used by Conolly et al. (ibid.) was extended to humans. Regional dosimetry predictions for the entire respiratory tract were obtained by merging a three-dimensional CFD model for the human nose with a one-dimensional typical path model for the lower respiratory tract. In other respects, the human model was structurally identical to the rat model. The predicted human dose response for DPX was obtained by scale-up of a computational model for DPX calibrated against rat and rhesus monkey data. The rat dose response for CRCP was used "as is" for the human model, since no preferable alternative was identified. Three

  18. The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice.

    PubMed

    Shaheen, Hazem M; Onoda, Atsuto; Shinkai, Yusuke; Nakamura, Masayuki; El-Ghoneimy, Ashraf A; El-Sayed, Yasser S; Takeda, Ken; Umezawa, Masakazu

    2016-10-01

    Recent studies have suggested that inhalation of diesel exhaust (DE), a major source of air pollution, results in pulmonary alterations; however, the effects of DE at low concentrations are poorly understood. Therefore, this study was conducted to elucidate the pulmonary effects of low-level exposure to DE and the potential role of a ceramide de novo biosynthesis inhibitor, fumonisin B1 (FB1) to ameliorate the DE-toxicity. Male C57BL/6J mice underwent 1- or 7-day experiments (4 equal groups/experiment) and were assigned to the control, DE (0.1mg/m(3)), FB1 (6.75mg/kg body weight SC at days 0, 3 and 6) or DE+FB1 groups. DE and/or FB1 treatment had no effect on the expression of Nos2, a biomarker of oxidative stress. Ceramide production in the bronchial epithelial cells and Sphk1 mRNA expression were induced in the lung after the 7-day DE exposure and were partially suppressed by the FB1 treatment. Additionally, the effects of DE on SP-A and SP-D mRNA expression were also suppressed by the FB1 treatment. These results suggest that ceramide and Sphk1 may be sensitive biomarkers for low-level DE-induced pulmonary effects. Collectively, ceramide likely contributes to the DE-induced early stage of airway inflammation, which is considered a potential pulmonary target during low-level DE exposure. PMID:27376354

  19. Long-term dose-response studies of inhaled or injected radionuclides. Biennial report, 1 October 1991--30 September 1993

    SciTech Connect

    Boecker, B.B.; Muggenburg, B.A.; Miller, S.C.; Bradley, P.L.

    1994-01-01

    This report describes the scientific progress in, and current status of, life-span studies of the long-term health risks in Beagle dogs of chronic irradiation from internally deposited radionuclides or from an external source. The reporting period for this document is the 2-year period from October 1, 1991 through September 30, 1993. Studies that were initiated at three different laboratories (Inhalation Toxicology Research Institute, ITRI, University of Utah, and Argonne National Laboratory, ANL) are presented here because they are being completed at ITRI. All living dogs in the Utah-initiated studies were transferred to the ITRI facility for the remainder of their life-span observations and measurements in September 1987. This report is the fourth in a series of reports dealing with the current status and progress of both the Utah and ITRI studies. Other life-span studies involving dogs exposed to gamma radiation from an external source were initiated and conducted for many years at ANL. In 1991, the decision was made to discontinue the chronic irradiation of the remaining living dogs and to transfer all remaining dogs to ITRI for care, clinical observations, and pathological observations at death or euthanasia. This report provides the current status of these dogs. Status reports on the Utah and ITRI studies comprise most of this report. The ITRI-related section presents brief statements of project objectives, the general procedures used in these studies, and some study-specific features for each of the 19 studies being conducted with either beta- or alpha-emitting radionuclides. Dose- and effect-modifying factors being addressed in these studies include total dose, dose rate, LET, solubility, nonuniformity of dose, species, age, sex, health status, and mode of exposure. Recent additions to experimental protocols for studies in which dogs are still alive involve the collection and analysis of tumor tissues using currently available molecular biology techniques.

  20. 40 CFR 721.10298 - MDI terminated polyester polyurethane polymer (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... polymer (generic). 721.10298 Section 721.10298 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10298 MDI terminated polyester polyurethane polymer (generic). (a... generically as MDI terminated polyester polyurethane polymer (P-11-662) is subject to reporting under...

  1. 40 CFR 721.10298 - MDI terminated polyester polyurethane polymer (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... polymer (generic). 721.10298 Section 721.10298 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10298 MDI terminated polyester polyurethane polymer (generic). (a... generically as MDI terminated polyester polyurethane polymer (P-11-662) is subject to reporting under...

  2. 40 CFR 721.10298 - MDI terminated polyester polyurethane polymer (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... polymer (generic). 721.10298 Section 721.10298 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10298 MDI terminated polyester polyurethane polymer (generic). (a... generically as MDI terminated polyester polyurethane polymer (P-11-662) is subject to reporting under...

  3. Effects of roflumilast in COPD patients receiving inhaled corticosteroid/long-acting β2-agonist fixed-dose combination: RE2SPOND rationale and study design

    PubMed Central

    Rennard, Stephen I; Martinez, Fernando J; Rabe, Klaus F; Sethi, Sanjay; Pizzichini, Emilio; McIvor, Andrew; Siddiqui, Shahid; Anzueto, Antonio; Zhu, Haiyuan

    2016-01-01

    Background Roflumilast, a once-daily, selective phosphodiesterase-4 inhibitor, reduces the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The RE2SPOND study is examining whether roflumilast, when added to an inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fixed-dose combination (FDC), further reduces exacerbations. The methodology is described herein. Methods In this Phase IV, multicenter, double-blind, placebo-controlled, parallel-group trial, participants were randomized 1:1 (stratified by long-acting muscarinic antagonist use) to receive roflumilast or placebo, plus ICS/LABA FDC, for 52 weeks. Eligible participants had severe COPD associated with chronic bronchitis, had two or more moderate–severe exacerbations within 12 months, and were receiving ICS/LABA FDC for ≥3 months. The primary efficacy measure is the rate of moderate or severe COPD exacerbations per participant per year. The secondary efficacy outcomes include mean change in prebronchodilator forced expiratory volume in 1 second (FEV1) over 52 weeks, rate of severe exacerbations, and rate of moderate, severe, or antibiotic-treated exacerbations. Additional assessments include spirometry, rescue medication use, the COPD assessment test, daily symptoms using the EXACT-Respiratory symptoms (E-RS) questionnaire, all-cause and COPD-related hospitalizations, and safety and pharmacokinetic measures. Results Across 17 countries, 2,354 participants were randomized from September 2011 to October 2014. Enrollment goal was met in October 2014, and study completion occurred in June 2016. Conclusion This study will further characterize the effects of roflumilast added to ICS/LABA on exacerbation rates, lung function, and health of severe–very severe COPD participants at risk of further exacerbations. The results will determine the clinical benefits of roflumilast combined with standard-of-care inhaled COPD treatment. PMID

  4. Biological characterization of radiation exposure and dose estimates for inhaled uranium milling effluents. Annual progress report April 1, 1982-March 31, 1983

    SciTech Connect

    Eidson, A.F.

    1984-05-01

    The problems addressed are the protection of uranium mill workers from occupational exposure to uranium through routine bioassay programs and the assessment of accidental worker exposures. Comparisons of chemical properties and the biological behavior of refined uranium ore (yellowcake) are made to identify important properties that influence uranium distribution patterns among organs. These studies will facilitate calculations of organ doses for specific exposures and associated health risk estimates and will identify important bioassay procedures to improve evaluations of human exposures. A quantitative analytical method for yellowcake was developed based on the infrared absorption of ammonium diuranate and U/sub 3/O/sub 8/ mixtures in KBr. The method was applied to yellowcake samples obtained from six operating mills. The composition of yellowcake from the six mills ranged from nearly pure ammonium diuranate to nearly pure U/sub 3/O/sub 8/. The composition of yellowcake samples taken from lots from the same mill was only somewhat less variable. Because uranium mill workers might be exposed to yellowcake either by contamination of a wound or by inhalation, a study of retention and translocation of uranium after subcutaneous implantation in rats was done. The results showed that 49% of the implanted yellowcake cleared from the body with a half-time (T sub 1/2) in the body of 0.3 days, and the remainder was cleared with a T sub 1/2 of 11 to 30 days. Exposures of Beagle dogs by nose-only inhalation to aerosols of commercial yellowcake were completed. Biochemical indicators of kidney dysfunction that appeared in blood and urine 4 to 8 days after exposure to the more soluble yellowcake showed significant changes in dogs, but levels returned to normal by 16 days after exposure. No biochemical evidence of kidney dysfunction was observed in dogs exposed to the less soluble yellowcake form. 18 figures, 9 tables.

  5. Computational modeling as part of alternative testing strategies in the respiratory and cardiovascular systems: inhaled nanoparticle dose modeling based on representative aerosol measurements and corresponding toxicological analysis.

    PubMed

    Pilou, Marika; Mavrofrydi, Olga; Housiadas, Christos; Eleftheriadis, Kostas; Papazafiri, Panagiota

    2015-05-01

    The objectives of modeling in this work were (a) the integration of two existing numerical models in order to connect external exposure to nanoparticles (NPs) with internal dose through inhalation, and (b) to use computational fluid-particle dynamics (CFPD) to analyze the behavior of NPs in the respiratory and the cardiovascular system. Regarding the first objective, a lung transport and deposition model was combined with a lung clearance/retention model to estimate NPs dose in the different regions of the human respiratory tract and some adjacent tissues. On the other hand, CFPD was used to estimate particle transport and deposition of particles in a physiologically based bifurcation created by the third and fourth lung generations (respiratory system), as well as to predict the fate of super-paramagnetic particles suspended in a liquid under the influence of an external magnetic field (cardiovascular system). All the above studies showed that, with proper refinement, the developed computational models and methodologies may serve as an alternative testing strategy, replacing transport/deposition experiments that are expensive both in time and resources and contribute to risk assessment. PMID:24295373

  6. Motion-compensated PET image reconstruction with respiratory-matched attenuation correction using two low-dose inhale and exhale CT images

    NASA Astrophysics Data System (ADS)

    Nam, Woo Hyun; Ahn, Il Jun; Kim, Kyeong Min; Kim, Byung Il; Ra, Jong Beom

    2013-10-01

    Positron emission tomography (PET) is widely used for diagnosis and follow up assessment of radiotherapy. However, thoracic and abdominal PET suffers from false staging and incorrect quantification of the radioactive uptake of lesion(s) due to respiratory motion. Furthermore, respiratory motion-induced mismatch between a computed tomography (CT) attenuation map and PET data often leads to significant artifacts in the reconstructed PET image. To solve these problems, we propose a unified framework for respiratory-matched attenuation correction and motion compensation of respiratory-gated PET. For the attenuation correction, the proposed algorithm manipulates a 4D CT image virtually generated from two low-dose inhale and exhale CT images, rather than a real 4D CT image which significantly increases the radiation burden on a patient. It also utilizes CT-driven motion fields for motion compensation. To realize the proposed algorithm, we propose an improved region-based approach for non-rigid registration between body CT images, and we suggest a selection scheme of 3D CT images that are respiratory-matched to each respiratory-gated sinogram. In this work, the proposed algorithm was evaluated qualitatively and quantitatively by using patient datasets including lung and/or liver lesion(s). Experimental results show that the method can provide much clearer organ boundaries and more accurate lesion information than existing algorithms by utilizing two low-dose CT images.

  7. Rheology and microstructure of MDI PEG reactive prepolymer-modified bitumen

    NASA Astrophysics Data System (ADS)

    Navarro, F. J.; Partal, P.; Martínez-Boza, F.; Gallegos, C.; Bordado, J. C. M.; Diogo, A. C.

    2006-12-01

    This paper deals with the use of a new bitumen modifier, a reactive prepolymer, based on the reaction of 4,4‧-diphenylmethane diisocyanate (MDI) and a low molecular weight polyethylene glycol (PEG). The rheological and thermal behaviours of modified bitumen containing a low MDI PEG concentration, as well as its morphology, have been studied. A relatively low amount of MDI PEG (0.5 to 1.5% wt.) yields a significant improvement in the modified bitumen rheological properties, mainly in the high in-service temperature region. In this range of temperature, the rheological properties are clearly affected by curing time at room temperature. These results indicate that chemical changes, due to the reaction of MDI isocyanate groups with the most polar groups ( OH; NH) of asphaltenes and resins, are produced. Thus, new chemical structures, non-visible by optical microscopy, slowly develop in MDI PEG modified bitumen when samples are cured at room temperature.

  8. Facular-sunspot coverage relation derived by MDI magnetograms

    NASA Astrophysics Data System (ADS)

    Criscuoli, Serena

    2016-05-01

    We employ MDI full-disk magnetograms acquired during Cycle 23 and at the beginning of Cycle 24 to investigate the relation between the filling factor of magnetic elements characterized by different amount of magnetic flux and located at different angular distance from disk center with the sunspot number. In agreement with some previous studies we find that daily data are best described by a quadratic function while data averaged over 6-months are best described by a linear function. In both cases the coefficients of the fits show large dependence on the position over the disk and the magnetic flux. We also find that toward disk center 6-months averaged data show asymmetries between the ascending and the descending phase.

  9. Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    EPA Science Inventory

    Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

  10. Asthma Inhalers

    MedlinePlus

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