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Sample records for dose inhaler mdi

  1. Skill development regarding use of metered dose inhaler (MDI) amongst school teachers of northern India.

    PubMed

    Kumar, Ashok; Singh, Neena Vir; Kaur, Sukhpal; Singh, Amarjeet

    2013-11-01

    To evaluate the impact of a booklet based training by a nurse on the development of skills regarding use of metered dose inhaler (MDI) among the teachers of the selected schools of Chandigarh, India. The present study was undertaken by randomly selecting government schools of Chandigarh from where 91 school teachers were enrolled. A booklet on asthma management containing information regarding asthma, its triggers, signs and symptoms, treatment, types of inhalers and steps of using MDI with spacer was used for training the subjects. Their knowledge and skills were evaluated through observation checklist. Three return demonstrations were taken from each teacher on three successive days. Main outcome measure was skill development of the teachers in the use of MDI with spacer. Pre and post tests scores were compared by repeated measures ANOVA. Most of the teachers didn't know theoretical or practical aspects of MDI. After training all the teachers performed correctly most of the steps of MDI use. Some teachers performed poorly in giving instruction to breathe in/out slowly and hand washing before/after MDI administration. There was a statistical significant improvement in the performance scores of the teachers after each return demonstration (p < 0.0005). Training strategy used in the study involving nursing personnel was successful in improving teachers' skills in MDI use for asthma management. More focus should be given on breathe in/out instructions and on hand washing before/after MDI use.

  2. 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.

  3. The influence of actuator materials and nozzle designs on electrostatic charge of pressurised metered dose inhaler (pMDI) formulations.

    PubMed

    Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

    2014-05-01

    To investigate the influence of different actuator materials and nozzle designs on the electrostatic charge properties of a series of solution metered dose inhaler (pMDI) aerosols. Actuators were manufactured with flat and cone nozzle designs using five different materials from the triboelectric series (Nylon, Polyethylene terephthalate, Polyethylene-High density, Polypropylene copolymer and Polytetrafluoroethylene). The electrostatic charge profiles of pMDI containing beclomethasone dipropionate (BDP) as model drug in HFA-134a propellant, with different concentrations of ethanol were studied. Electrostatic measurements were taken using a modified electrical low-pressure impactor (ELPI) and the deposited drug mass assayed chemically using HPLC. The charge profiles of HFA 134a alone have shown strong electronegativity with all actuator materials and nozzle designs, at an average of -1531.34 pC ± 377.34. The presence of co-solvent ethanol significantly reduced the negative charge magnitude. BDP reduced the suppressing effect of ethanol on the negative charging of the propellant. For all tested formulations, the flat nozzle design showed no significant differences in net charge between different actuator materials, whereas the charge profiles of cone designs followed the triboelectric series. The electrostatic charging profiles from a solution pMDI containing BDP and ethanol can be significantly influenced by the actuator material, nozzle design and formulation components. Ethanol concentration appears to have the most significant impact. Furthermore, BDP interactions with ethanol and HFA have an influence on the electrostatic charge of aerosols. By choosing different combinations of actuator materials and orifice design, the fine particle fractions of formulations can be altered.

  4. Asthma patients' inability to use a pressurised metered-dose inhaler (pMDI) correctly correlates with poor asthma control as defined by the global initiative for asthma (GINA) strategy: a retrospective analysis.

    PubMed

    Levy, Mark L; Hardwell, Alison; McKnight, Eddie; Holmes, John

    2013-12-01

    In practice it is logical that inhalers are prescribed only after patients have received training and demonstrated their ability to use the device. However, many patients are unable to use their pressurised metered-dose inhaler devices (pMDIs) correctly. We assessed the relationship between asthma control and patients' ability to use their prescribed pMDIs. Evaluation of 3,981 (46% male) primary care asthma patient reviews, which included inhaler technique and asthma control, by specialist nurses in primary care in 2009. The paper focuses on people currently prescribed pMDI devices. Accurate data on reliever and preventer inhaler prescriptions were available for 3,686 and 2,887 patients, respectively. In patients prescribed reliever inhalers, 2,375 (64%) and 525 (14%) were on pMDI alone or pMDI plus spacer, respectively. For those prescribed preventers, 1,976 (68%) and 171 (6%) were using a pMDI without and with a spacer, respectively. Asthma was controlled in 50% of patients reviewed. The majority of patients (60% of 3,686) were using reliever pMDIs, 13% with spacers. Incorrect pMDI use was associated with poor asthma control (p<0.0001) and more short burst systemic steroid prescriptions in the last year (p=0.038). Of patients using beclometasone (the most frequently prescribed preventer drug in our sample), significantly more of those using a breath-actuated pMDI device (p<0.0001) and a spacer (p<0.0001) were controlled compared with those on pMDIs alone. Patients who are able to use pMDIs correctly have better asthma control as defined by the GINA strategy document. Beclometasone via a spacer or breath-actuated device resulted in better asthma control than via a pMDI alone. Patients prescribed pMDIs should be carefully instructed in technique and have their ability to use these devices tested; those unable to use the device should be prescribed a spacer or an alternative device such as one that is breath-actuated.

  5. Efficacy and safety of ipratropium bromide/albuterol delivered via Respimat inhaler versus MDI.

    PubMed

    Zuwallack, R; De Salvo, M C; Kaelin, T; Bateman, E D; Park, C S; Abrahams, R; Fakih, F; Sachs, P; Pudi, K; Zhao, Y; Wood, C C

    2010-08-01

    We compared the efficacy and safety of ipratropium bromide/albuterol delivered via Respimat inhaler, a novel propellant-free inhaler, versus chlorofluorocarbon (CFC)-metered dose inhaler (MDI) and ipratropium Respimat inhaler in patients with COPD. This was a multinational, randomized, double-blind, double-dummy, 12-week, parallel-group, active-controlled study. Patients with moderate to severe COPD were randomized to ipratropium bromide/albuterol (20/100mcg) Respimat inhaler, ipratropium bromide/albuterol MDI [36mcg/206mcg (Combivent Inhalation Aerosol MDI)], or ipratropium bromide (20mcg) Respimat inhaler. Each medication was administered four times daily. Serial spirometry was performed over 6h (0.15min, then hourly) on 4 test days. The primary efficacy variable was forced expiratory volume in 1s (FEV(1)) change from test day baseline at 12 weeks. A total of 1209 of 1480 randomized, treated patients completed the study; the majority were male (65%) with a mean age of 64 yrs and a mean screening pre-bronchodilator FEV(1) (percent predicted) of 41%. Ipratropium bromide/albuterol Respimat inhaler had comparable efficacy to ipratropium bromide/albuterol MDI for FEV(1) area under the curve at 0-6h (AUC(0-6)), superior efficacy to ipratropium Respimat inhaler for FEV(1) AUC(0-4) and comparable efficacy to ipratropium Respimat inhaler for FEV(1) AUC(4-6). All active treatments were well tolerated. This study demonstrates that ipratropium bromide/albuterol 20/100mcg inhaler administered four times daily for 12 weeks had equivalent bronchodilator efficacy and comparable safety to ipratropium bromide/albuterol 36mcg/206mcg MDI, and significantly improved lung function compared with the mono-component ipratropium bromide 20 mcg Respimat inhaler. [Clinical Trial Identifier Number: NCT00400153].

  6. Therapeutic equivalence of budesonide/formoterol delivered via breath-actuated inhaler vs pMDI.

    PubMed

    Murphy, Kevin R; Dhand, Rajiv; Trudo, Frank; Uryniak, Tom; Aggarwal, Ajay; Eckerwall, Göran

    2015-02-01

    To assess equivalence of twice daily (bid) budesonide/formoterol (BUD/FM) 160/4.5 μg via breath-actuated metered-dose inhaler (BAI) versus pressurized metered-dose inhaler (pMDI). This 12-week, double-blind, multicenter, parallel-group study, randomized adolescents and adults (aged ≥12 years) with asthma (and ≥3 months daily use of inhaled corticosteroids) to BUD/FM BAI 2 × 160/4.5 μg bid, BUD/FM pMDI 2 × 160/4.5 μg bid, or BUD pMDI 2 × 160 μg bid. Inclusion required prebronchodilator forced expiratory volume in one second (FEV1) ≥45 to ≤85% predicted, and reversibility of ≥12% in FEV1 (ages 12 to <18 years) or ≥12% and 200 mL (ages ≥18 years). Confirmation that 60-min postdose FEV1 response to BUD/FM pMDI was superior to BUD pMDI was required before equivalence testing. Therapeutic equivalence was shown by treatment effect ratio of BUD/FM BAI vs BUD/FM pMDI on 60-min postdose FEV1 and predose FEV1 within confidence intervals (CIs) of 80-125%. Mean age of 214 randomized patients was 42.7 years. BUD/FM pMDI was superior to BUD pMDI (60-min postdose FEV1 treatment effect ratio, 1.10; 95% CI, 1.06-1.14; p < 0.001). Treatment effect ratios for BUD/FM BAI versus pMDI for 60-min postdose FEV1 (1.01; 95% CI, 0.97-1.05) and predose FEV1 (1.03; 95% CI, 0.99-1.08) were within predetermined CIs for therapeutic equivalence. Adverse event profiles, tolerability, and patient-reported ease of use were similar. BUD/FM 2 × 160/4.5 μg bid BAI is therapeutically equivalent to BUD/FM conventional pMDI. The introduction of BUD/FM BAI would expand options for delivering inhaled corticosteroid/long-acting β2-agonist combination therapy to patients with moderate-to-severe asthma. ClinicalTrials.gov NCT01360021. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Early bronchodilatory effects of budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and albuterol pMDI: 2 randomized controlled trials in adults with persistent asthma previously treated with inhaled corticosteroids.

    PubMed

    Hampel, Frank C; Martin, Paula; Mezzanotte, William S

    2008-05-01

    Two identically designed, randomized, multicenter, single-dose, crossover studies were conducted in patients aged > or = 18 years with mild to moderate asthma previously treated with inhaled corticosteroids. After 2 weeks on twice-daily budesonide pressurized metered-dose inhaler (pMDI) 160 microg, patients received a randomized sequence of budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), fluticasone/salmeterol dry powder inhaler (DPI) 250/50 microg x 1 inhalation, albuterol pMDI 90 microg x 2 inhalations (180 microg), and placebo pMDI (3-to 14-day washout periods). Improvements in forced expiratory volume in 1 second (FEV(1)) at 3 minutes were significantly (p < 0.001) greater after treatment with budesonide/formoterol pMDI compared with fluticasone/salmeterol DPI and similar to that of albuterol pMDI. In addition, significantly (p < 0.001) more patients treated with budesonide/formoterol pMDI achieved a 15% improvement in FEV(1) within 15 minutes compared with patients treated with fluticasone/salmeterol DPI and placebo. Thus, the early bronchodilatory effects of budesonide/formoterol pMDI were greater than with fluticasone/salmeterol DPI.

  8. Higher lung deposition with Respimat Soft Mist inhaler than HFA-MDI in COPD patients with poor technique.

    PubMed

    Brand, Peter; Hederer, Bettina; Austen, George; Dewberry, Helen; Meyer, Thomas

    2008-01-01

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

  9. The abbreviated impactor measurement (AIM) concept: part 1--Influence of particle bounce and re-entrainment-evaluation with a "dry" pressurized metered dose inhaler (pMDI)-based formulation.

    PubMed

    Mitchell, J P; Nagel, M W; Avvakoumova, V; MacKay, H; Ali, R

    2009-01-01

    The abbreviated impactor measurement concept is a potential improvement to the labor-intensive full-resolution cascade impactor methodology for inhaler aerosol aerodynamic particle size distribution (APSD) measurement by virtue of being simpler and therefore quicker to execute. At the same time, improved measurement precision should be possible by eliminating stages upon which little or no drug mass is collected. Although several designs of abbreviated impactor systems have been developed in recent years, experimental work is lacking to validate the technique with aerosols produced by currently available inhalers. In part 1 of this two-part article that focuses on aerosols produced by pressurized metered dose inhalers (pMDIs), the evaluation of two abbreviated impactor systems (Copley fast screening Andersen impactor and Trudell fast screening Andersen impactor), based on the full-resolution eight-stage Andersen nonviable cascade impactor (ACI) operating principle, is reported with a formulation producing dry particles. The purpose was to investigate the potential for non-ideal collection behavior associated with particle bounce in relation to internal losses to surfaces from which particles containing active pharmaceutical ingredient are not normally recovered. Both abbreviated impactors were found to be substantially equivalent to the full-resolution ACI in terms of extra-fine and fine particle and coarse mass fractions used as metrics to characterize the APSD of these pMDI-produced aerosols when sampled at 28.3 L/min, provided that precautions are taken to coat collection plates to minimize bounce and entrainment.

  10. A randomized study of tiotropium Respimat Soft Mist inhaler vs. ipratropium pMDI in COPD.

    PubMed

    Voshaar, T; Lapidus, R; Maleki-Yazdi, R; Timmer, W; Rubin, E; Lowe, L; Bateman, E

    2008-01-01

    The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat Soft Mist Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 microg) via Respimat SMI administered once daily, ipratropium (36 microg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1s (FEV(1)) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV(1) (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 microg and placebo for the primary endpoint (mean trough FEV(1) response at week 12) were 0.118 and 0.149L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 microg and ipratropium were 0.064L (P=0.006) and 0.095L (P<0.0001). The increases in peak FEV(1), FEV(1) AUC((0-6h)) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 microg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 microg daily, delivered via Respimat SMI, significantly improved lung function compared with ipratropium pMDI and placebo.

  11. Comparison of salbutamol efficacy in children--via the metered-dose inhaler (MDI) with Volumatic spacer and via the dry powder inhaler, Easyhaler, with the nebulizer--in mild to moderate asthma exacerbation: a multicenter, randomized study.

    PubMed

    Direkwatanachai, Chalerat; Teeratakulpisarn, Jamaree; Suntornlohanakul, Somchai; Trakultivakorn, Muthita; Ngamphaiboon, Jarungchit; Wongpitoon, Nares; Vangveeravong, Mukda

    2011-03-01

    Beta(2) agonist administered via a nebulizer is the standard treatment for acute asthma exacerbation. There are some limitations for the use of nebulization. We conducted a study to determine the efficacy of salbutamol administered via the pMDI with Volumatic spacer and the Easyhaler (DPI) compared to nebulization in mild to moderate asthma exacerbations in children. A multicenter, randomized, controlled study was conducted in children between 5 and 18 years of age who presented at an emergency or outpatient department. They were randomized to receive either 6 puffs of salbutamol via the pMDI with Volumatic spacer, or via the Easyhaler, or 0.15 mg/kg of salbutamol nebulized via oxygen (or compressed air). The primary outcome was the clinical response which was assessed using the modified Wood's asthma score. The secondary outcomes were: hospitalization, asthma revisit within 3 days, systemic corticosteroid use and adverse events. The clinical score, oxygen saturation, PR, RR, BP and adverse events were recorded at time 0 (before treatment) and 20, 40 and 60 minutes after drug administration. There were no statistically significant differences in the clinical response between the three groups at the 1st, 2nd or 3rd dose or for the SpO(2) or the respiratory rate while the children in the Easyhaler group had significantly less tachycardia after the 2nd dose. No significant adverse events were noted among the three groups. Salbutamol administered via pMDI with Volumatic spacer or DPI (Easyhaler) are as effective as salbutamol given via a nebulizer in providing effective relief of mild to moderate severity acute asthma exacerbation in children between 5 and 18 years of age.

  12. 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.

  13. EXAMINATION OF THE EFFECTIVENESS OF SLOW AND DEEP INHALATION OF FP/FM-pMDI FOR THE SMALL-AIRWAYS DYSFUNCTION OF ADULT-ONSET ASTHMA.

    PubMed

    Hashimoto, Shoji

    To date adult-onset asthmatic patients who lack a clear stridor and show prolonged coughs and chest discomfort caused by small-airways dysfunction have increased. We examined the small-airways function of these cases and the effectiveness of slow and deep inhalation of FP/FM-pMDI. 62 adult-onset asthmatic patients who had prolonged coughs and chest discomfort with the middle or high dose of ICS/LABA combination agents under well technique (32 of BUD/FM-DPI group and 30 of FP/SM-pMDI group) were included into this study. ICS/LABAs were switched to FP/FM-pMDI and slow and deep inhalation for 2-3 seconds was carried out thoroughly. The dose of FP/FM-pMDI was reduced depending on the improvement of symptoms. ACT score, respiratory function tests and respiratory resistance were measured after approximately six months from switching (stable condition after switching) and were compared with the values of the same period of the last year (stable condition under the previous ICS/LABA). After switching to FP/FM-pMDI, asthmatic symptoms and plural values of small-airways function were improved in 93.7% (30/32 cases) of BUD/FM-DPI group and in 86.6% (26/30 cases) of FP/SM-pMDI group. Moreover, mean daily inhalation doses were decreased from 5.0 to 4.3 in BUD/FM-DPI group and decreased from 5.7 to 3.7 in FP/SM-pMDI group. Slow and deep inhalation of FP/FM-pMDI is effective in many asthmatic patients who have prolonged small-airways dysfunction. A prospective, multi-centered contrastive study is warranted to confirm the effectiveness of this inhalational method.

  14. Double-blind, double-dummy, multinational, multicenter, parallel-group design clinical trial of clinical non-inferiority of formoterol 12 microg/unit dose in a b.i.d. regimen administered via an HFA-propellant-pMDI or a dry powder inhaler in a 12-week treatment period of moderate to severe stable persistent asthma in adult patients.

    PubMed

    Dusser, D; Vicaut, E; Lefrançois, G

    2005-01-01

    Pressurized metered-dose inhalers (pMDIs) have traditionally used CFCs as propellants. However, the worldwide phase-out of CFCs has necessitated the development of new pMDIs that use alternative propellants. One such replacement is the hydrofluoroalkane HFA-134a. This study sought to establish the clinical non-inferiority of a new HFA-134a-containing pMDI to a conventional dry powder inhaler (DPI) in the administration of formoterol to adult patients with moderate-to-severe, stable persistent asthma. The secondary aim was to collect safety data in a multiple-dose long-term study. During this multicenter, double-blind, parallel study, 500 patients were randomized to receive 12 microg of formoterol twice daily for 12 weeks via either an HFA pMDI or a DPI. If necessary, the dose could be increased to 24 microg twice daily. At baseline, all patients (aged 18-70 years) had an FEV1 40-80% of predicted and a documented positive response to the reversibility test. After 12 weeks' therapy, the adjusted mean morning PEFR was 343.69 l/min in the formoterol HFA pMDI group and 344.56 l/min in the formoterol DPI group. Because the lower limit of the 95% CI for the between-group difference (-11.64 l/min) was well within the non-inferiority margin (-20 l/min), the HFA device was deemed clinically non-inferior to the DPI device. This finding was confirmed when evening PEFR and FEV1 were assessed. Both formulations of formoterol were well tolerated during prolonged multiple dosing. This study provides evidence that the new HFA-formulated formoterol pMDI has a similar efficacy and safety profile to the conventional formoterol DPI in the treatment of patients with moderate-to-severe asthma.

  15. Inhaled corticosteroid metered-dose inhalers: how do variations in technique for solutions versus suspensions affect drug distribution?

    PubMed

    Robinson, Christie A; Tsourounis, Candy

    2013-03-01

    To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions. PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed. All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified. Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs. Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.

  16. Micronuclei, hemoglobin adducts and respiratory tract irritation in mice after inhalation of toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI).

    PubMed

    Lindberg, Hanna K; Korpi, Anne; Santonen, Tiina; Säkkinen, Kirsi; Järvelä, Merja; Tornaeus, Jarkko; Ahonen, Niina; Järventaus, Hilkka; Pasanen, Anna-Liisa; Rosenberg, Christina; Norppa, Hannu

    2011-07-14

    Toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI), used in the production of polyurethane foam, are well known for their irritating and sensitizing properties. Contradictory results have been obtained on their genotoxicity. We investigated the genotoxicity and protein binding of inhaled TDI and MDI in mice by examining micronucleated polychromatic erythrocytes (PCEs) in bone marrow and peripheral blood and TDI- and MDI-derived adducts in hemoglobin. Male C57Bl/6J mice (8 per group) were exposed head-only to TDI vapour (mean concentrations 1.1, 1.5, and 2.4mg/m(3); the mixture of isomers contained, on the average, 63% 2,4-TDI and 37% 2,6-TDI) or MDI aerosol (mean concentrations 10.7, 20.9 and 23.3mg/m(3)), during 1h/day for 5 consecutive days. Bone marrow and peripheral blood were collected 24h after the last exposure. Inhalation of TDI caused sensory irritation (SI) in the upper respiratory tract, and cumulative effects were observed at the highest exposure level. Inhalation of MDI produced SI and airflow limitation, and influx of inflammatory cells into the lungs. Hemoglobin adducts detected in the exposed mice resulted from direct binding to globin of 2,4- and 2,6-TDI and MDI, and dose-dependent increases were observed especially for 2,4-TDI-derived adducts. Adducts originating from the diamines of TDI (toluene diamine) or MDI (methylene dianiline) were not observed. No significant increase in the frequency of micronucleated PCEs was detected in the bone marrow or peripheral blood of the mice exposed to TDI or MDI. The ratio of PCEs and normochromatic erythrocytes (NCEs) was reduced at the highest concentration of MDI, and a slight reduction of the PCE/NCE ratio, dependent on cumulative inhaled dose, was also seen with TDI. Our results indicate that inhalation of TDI or MDI (1h/day for 5 days), at levels that induce toxic effects and formation of TDI- or MDI-specific adducts in hemoglobin, does not have detectable genotoxic effects in mice

  17. [Isobutane driven salbutamol sulfate metered dose inhaler: formulation selection and respiratory tract absorption in guinea pigs].

    PubMed

    Ding, Li; Zhang, Jun-Shou

    2009-09-01

    This paper is to study the iso-butane (A-31)-driven salbutamol sulfate (SS) metered dose inhaler (MDI) formulations and inhaling status in guinea pigs. Solubility determination and orthogonal design were used to screen non-chlorofluorocarbon (CFC) SS MDI formulations. Intubation inhalation of MDI in guinea pigs was used as a main administration method. Fluorescence HPLC detection method was testified as a potential method in assaying the concentration of SS in plasma of guinea pigs after inhaling various SS MDI formulations. Analysis of the data was executed with statistical moment calculation from which pharmacokinetic parameters were obtained. The results show that A-31 based on SS MDI formulations were screened and the guinea pigs in vivo determination method after inhaling SS MDI was established. The zero-moment rations of SS/A-31 MDI formulation to contrast sample and CFC SS MDI was 143.26% and 147.01%, respectively. The first moment value of SS/A-31 MDI formulation was the highest. It is a preliminary conclusion that the absorption result of SS/A-31 MDI formulation inhaled by guinea pigs is equivalent to HFA-134a formulation in sale and better than CFC formulation. A-31 could be used as a potential substitute candidate for CFC MDI propellant.

  18. Concurrent use of metered dose inhalers without spacer and dry powder inhalers by asthmatic children adversely affect proper inhalation technique

    PubMed Central

    Alotaibi, Saad; Hassan, Walid M; Alhashimi, Hashim

    2011-01-01

    Asthma is a common chronic disease of children. A good control of symptoms will improve quality of patient life. Inhalation technique is an important aspect in the management of asthma. The better the inhalation technique the better the lung deposition of asthma therapy especially inhaled corticosteroids. This will lead to better control of symptoms and improve adherence to treatment. In the following study the inhalation technique of asthma devices were compared using inhalation technique score system. The asthma devices studied were metered dose inhalers (pressurized MDI) without spacers and dry powder inhalers (DPI). The hypothesis studied was that the inhalation technique score of dry powder inhalers will be adversely affected with concurrent use of metered dose inhalers without spacers. PMID:21760757

  19. Concurrent use of metered dose inhalers without spacer and dry powder inhalers by asthmatic children adversely affect proper inhalation technique.

    PubMed

    Alotaibi, Saad; Hassan, Walid M; Alhashimi, Hashim

    2011-06-14

    Asthma is a common chronic disease of children. A good control of symptoms will improve quality of patient life. Inhalation technique is an important aspect in the management of asthma. The better the inhalation technique the better the lung deposition of asthma therapy especially inhaled corticosteroids. This will lead to better control of symptoms and improve adherence to treatment. In the following study the inhalation technique of asthma devices were compared using inhalation technique score system. The asthma devices studied were metered dose inhalers (pressurized MDI) without spacers and dry powder inhalers (DPI). The hypothesis studied was that the inhalation technique score of dry powder inhalers will be adversely affected with concurrent use of metered dose inhalers without spacers.

  20. Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel, dry powder inhaler versus a prevailing dry powder inhaler and a metered-dose inhaler.

    PubMed

    Gillespie, Michael; Song, Sharon; Steinfeld, Jonathan

    2015-01-01

    A novel inhalation-driven multidose dry powder inhaler (MDPI) that eliminates the need for the patient to coordinate device actuation with inhalation has been developed for delivery of inhaled asthma medications. To characterize the pharmacokinetics of single-dose fluticasone propionate (Fp) MDPI compared with single doses of Fp dry powder inhaler (DPI) and a metered-dose inhaler (MDI) in healthy subjects. This was a single-center, open-label, randomized, three-period crossover, single-dose pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18) were randomized to one of six treatment sequences that contained three treatment arms: Fp MDPI 400 μg/inhalation × two inhalations (800 μg total dose); Fp DPI 250 μg/inhalation × four (1000 μg total dose); and Fp MDI 220 μg/inhalation × four (880 μg total dose). Pharmacokinetics (area under concentration-versus-time curve [AUC], maximum plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life [t½]), safety, and tolerability were assessed for each treatment. Plasma Fp concentration-versus-time curves were comparable across treatments. Geometric mean AUC0-t and Cmax for Fp MDPI 800 μg were 19% and 18% higher, respectively, compared with Fp DPI 1000 μg, and 47% and 82% higher, respectively, compared with Fp MDI 880 μg. Median tmax (60.0-60.6 minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three treatments. Single-dose Fp was well tolerated, with no new safety issues noted. Single-dose administration of Fp MDPI 800 μg produced systemic exposure comparable with those for Fp DPI 1000 μg and Fp MDI 880 μg.

  1. Adrenal suppression in asthmatic children receiving low-dose inhaled budesonide: comparison between dry powder inhaler and pressurized metered-dose inhaler attached to a spacer.

    PubMed

    Goldberg, Shmuel; Einot, Tsurit; Algur, Nurit; Schwartz, Shimshon; Greenberg, Alan C; Picard, Elie; Virgilis, Dov; Kerem, Eitan

    2002-12-01

    Dry powder inhalers (DPI) have in recent years become a common mode for administration of inhaled corticosteroids for preventive therapy of asthma. Inhaled steroids delivered by DPI achieve increased lung deposition compared with pressurized metered-dose inhalers (pMDI), which is associated with increased therapeutic effect. This may be associated with increased systemic absorption. The purpose of this study was to evaluate the prevalence of adrenal suppression in children using low-dose budesonide given by DPI, as compared with pMDI attached to a large-volume spacer device (pMDI + spacer). In an open-labeled crossover study, 15 asthmatic children aged 5 to 15 years received 200 microg of inhaled budesonide twice daily by DPI (Turbuhaler, Astra, Draco AB, Lund, Sweden) and by pMDI + spacer, 1 month each, in a randomized order. Twenty-four-hour urine collections were performed at baseline and at the end of each of the 2 months of the study period, and urinary cortisol and creatinine were measured. Baseline urinary cortisol:creatinine was 0.038 +/- 0.012 microg/mg, similar in both groups. After 1 month of DPI therapy, urinary cortisol:creatinine was reduced by 27 +/- 16% to 0.028 +/- 0.012 microg/mg (P = 0.018). Urinary cortisol:creatinine after 1 month of pMDI + spacer therapy was similar to baseline 0.037 +/- 0.019 microg/mg (P = 0.78). Treatment of asthmatic children with budesonide 400 microg daily given via a DPI for 1 month was associated with hypothalamic-pituitary-adrenal axis suppression. This effect was not observed with the same dose of budesonide administered via pMDI + spacer. This indicates that systemic absorption might be reduced with pMDI + spacer therapy.

  2. Concurrent use of metered-dose and dry powder inhalers by children with persistent asthma does not adversely affect spacer/inhaler technique.

    PubMed

    Chan, Debora S; Callahan, Charles W; Hatch-Pigott, Virginia B; Lawless, Annette; Proffitt, H Lorraine; Manning, Nola E; Schweikert, Mary P

    2006-10-01

    Studies conducted in adults have suggested that patients who use a metered-dose inhaler/holding chamber spacer (MDI/S) and dry powder inhaler (DPI) concurrently will have poorer MDI/S technique than that of patients who use MDI/S exclusively. To our knowledge, as of August 31, 2006, no studies have been performed in pediatric patients. To compare MDI/S technique scores of children using only MDI/S with scores of those using both MDI/S and DPIs. The MDI/S technique of children aged 6-17 years, with persistent asthma, recruited from a general pediatric practice population for an asthma intervention study project was scored using a standardized checklist. MDI/S scores of children who were being treated with maintenance and rescue medication delivered only by MDI/S were compared with those treated with both MDI/S (rescue) and DPI (maintenance). Scores lower than 70% were considered to be inadequate. A total of 117 patients (73 male, 44 female), aged 9.70 +/- 3.1 years (mean +/- SD), with persistent asthma, participated in the study. There were 83 children (54 male, 29 female, age 9.4 +/- 3.2 y) in the MDI/S only group and 34 (19 male, 15 female, age 10.3 +/- 2.9 y) in the MDI/S + DPI group. In the MDI/S + DPI group, Diskus was the DPI used for 32 patients, and Turbuhaler was used by 2 children. Sixteen patients had severe persistent asthma, 80 had moderate persistent asthma, and 21 had mild persistent asthma as classified by National Heart Lung and Blood Institute guidelines. No difference in sex and age demographics existed; however, there was a difference in the distribution of asthma severity between groups (ie, no patients with mild persistent asthma in the MDI/S + DPI group; p < or = 0.01). Mean score for the MDI/S only group was 86 +/- 17% and, for the MDI/S + DPI group, 90.1 +/- 12% (p = 0.15). More patients in the MDI/S group had inadequate scores (18%) compared with those in the MDI/S + DPI group (3%; p < 0.05). While DPI and MDI/S techniques are markedly

  3. The abbreviated impactor measurement (AIM) concept: part II--Influence of evaporation of a volatile component-evaluation with a "droplet-producing" pressurized metered dose inhaler (pMDI)-based formulation containing ethanol as cosolvent.

    PubMed

    Mitchell, J P; Nagel, M W; Avvakoumova, V; MacKay, H; Ali, R

    2009-01-01

    The abbreviated impactor measurement (AIM) concept is a potential solution to the labor-intensive full-resolution cascade impactor (CI) methodology for inhaler aerosol aerodynamic particle size measurement. In this validation study, the effect of increasing the internal dead volume on determined mass fractions relating to aerodynamic particle size was explored with two abbreviated impactors both based on the Andersen nonviable cascade impactor (ACI) operating principle (Copley fast screening Andersen impactor [C-FSA] and Trudell fast screening Andersen impactor [T-FSA]). A pressurized metered dose inhaler-delivered aerosol producing liquid ethanol droplets after propellant evaporation was chosen to characterize these systems. Measures of extrafine, fine, and coarse particle mass fractions from the abbreviated systems were compared with corresponding data obtained by a full-resolution ACI. The use of liquid ethanol-sensitive filter paper provided insight by rendering locations visible where partly evaporated droplets were still present when the "droplet-producing" aerosol was sampled. Extrafine particle fractions based on impactor-sized mass were near equivalent in the range 48.6% to 54%, comparing either abbreviated system with the benchmark ACI-measured data. The fine particle fraction of the impactor-sized mass determined by the T-FSA (94.4 +/- 1.7%) was greater than using the C-FSA (90.5 +/- 1.4%) and almost identical with the ACI-measured value (95.3 +/- 0.4%). The improved agreement between T-FSA and ACI is likely the result of increasing the dead space between the entry to the induction port and the uppermost impaction stage, compared with that for the C-FSA. This dead space is needed to provide comparable conditions for ethanol evaporation in the uppermost parts of these impactors.

  4. Valved Holding Chambers and In Vitro Metered Dose Inhaler Performance: Effects of Flow Rate and Inhalation Delay.

    PubMed

    Liu, Xiaofei; Guo, Changning; Chowdhury, Badrul; Starke, Peter; Limb, Susan; Peri, Prasad; Schroeder, Alan; Doub, William

    2017-08-28

    Multiple factors may influence the performance of a metered dose inhaler (MDI) when used with a valved holding chamber (VHC or "spacer"). Andersen Cascade Impactor measurements were conducted for three MDI products and two different VHCs using a specially designed system that accommodated variable delay times between MDI actuation and introduction of the aerosol into the impactor, and allowed reduced flow through the VHC while the impactor was operated at 28.3 L/min. Deposited drug mass and aerodynamic particle size distribution were determined using validated high-performance liquid chromatography (HPLC) methods. A two-level, three-factor full-factorial design of experiments (DOE) design was applied to assess the influences of VHC type, flow rate, and inhalation delay on a total of seven performance characteristics for each MDI product. An experiment without a VHC was added to assess the influence of VHC presence. DOE study shows the presence and type of VHC are the major influences on emitted dose and respirable fraction. Following the VHC effect, the inhalation delay has the most significant influence on most MDI performance metrics-emitted dose, respirable particle dose and fraction (aerosols between 1.1 and 4.7 μm), and fine particle dose and fraction (aerosols under 4.7 μm). This study illustrates the use of DOE analysis to effectively assess the effects of patient handling parameters (flow rate and inhalation delay) on the performance of MDI drugs when used with a VHC. The results of this study will inform Food and Drug Administration reviewers, the pharmaceutical industry, and healthcare practitioners as to safe and effective use of MDI products when used in conjunction with spacer devices.

  5. Brown Norway rat asthma model of diphenylmethane-4,4'-diisocyanate (MDI): determination of the elicitation threshold concentration of after inhalation sensitization.

    PubMed

    Pauluhn, Jürgen; Poole, Alan

    2011-03-15

    Occupational exposure to polymeric diphenylmethane-diisocyanate (MDI), a known human asthmagen, can be attributed to two potential routes: the skin and the respiratory tract. While the skin as the route of sensitization was the focus of a previous investigation (Pauluhn, 2008), this paper describes a modified sensitization protocol using a 5-day inhalation exposure (days 0-4) of Brown Norway (BN) rats to two concentration x exposure time (C x t) relationships of 1000, 5000, and 10,000 mg MDI/m³ x min at exposure durations of either 10 or 360-min. Apart from the differences in the induction protocol, all other experimental variables remained identical. This was followed by four 30-min inhalation challenges to 40 mg MDI/m³ on target days 20, 25, 50, and 65. After the last challenge, changes in breathing patterns delayed in onset were recorded and allergic lung inflammation was probed by bronchoalveolar lavage (BAL). In a subsequent study groups of rats were sensitized using the 10-min C x t protocol and challenged 3-times at 40 mg MDI/m³. At the fourth challenge a dose-escalation regimen was used to determine the elicitation threshold on 'asthmatic' rats. Consistent with the skin-sensitization protocol, the most sensitive endpoints characterizing an allergic pulmonary inflammation were again BAL-neutrophils and physiological measurements showing respiratory changes delayed in onset. The dose-escalation challenge yielded an elicitation threshold of 5 mg MDI-aerosol/m³ at 30 min challenge duration. In topically sensitized rats this threshold was estimated to be 3mg/m³. In summary, these data suggest the C x t product of MDI-aerosol that triggers an elicitation response in 'asthmatic' rats is slightly below of that causing acute pulmonary irritation in naïve rats. The high concentration delivered to the respiratory tract during the 10-min exposure period elicited a more vigorous response than the similar C x t at 360 min. Therefore, short high-level exposure

  6. 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.

  7. Efficacy of fluticasone metered-dose inhaler and dry powder inhaler for pediatric asthma.

    PubMed

    Miyahara, Hiroaki; Korematsu, Seigo; Nagakura, Tomokazu; Izumi, Tatsuro

    2008-02-01

    For the treatment of bronchial asthma, two types of fluticasone inhaler devices are available, namely, metered-dose inhaler with spacer (MDI-S) and the dry powder inhaler (DPI). The former is recommended for young children with a low peak inspiratory flow (PIF) and the latter for adolescents and adults. But the difference in the therapeutic efficacy between them has been studied only rarely in adolescent patients. In the present study, 21 post-elementary school-age patients with moderate persistent bronchial asthma (age 8-15 years, 10.3 +/- 2.1 years), who all had a sufficient PIF of 114 +/- 29 L/min, were examined in order to compare the two types of fluticasone inhalers. Eleven of 21 patients inhaled 200 microg/day Flutide using the MDI-S twice daily for 1 month in the first month, and the same dose using the DPI for the next month. The other 10 patients inhaled the opposite regimens. At the end of the each treatment, spirometry was examined. Measurements done before therapy and then at the end of MDI-S and DPI therapy, respectively, were as follows: forced expiratory volume in 1 s (FEV(1.0)), 72.4 +/- 18.2%, 91.5 +/- 18.2% and 84.1 +/- 16.3% (MDI-S vs DPI, P > 0.040); maximal mid-expiratory flow (MMEF), 62.0 +/- 23.6%, 88.7 +/- 26.5%, 79.3 +/- 33.4% (P > 0.044) and the peak expiratory flow (PEF) was 73.9 +/- 25.0%, 95.6 +/- 32.8%, and 90.5 +/- 29.5%, respectively (n.s.). MDI-S was thus found to be more effective in terms of %FEV(1.0) and in %MMEF. High therapeutic efficacy was obtained with the use of the MDI-S in fluticasone inhalation for post-elementary school-age patients with sufficient inspiration ability.

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

    PubMed

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

    2005-01-01

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

  9. How to Use Metered-Dose Inhalers

    MedlinePlus

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

  10. 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

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

    PubMed

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

    2015-02-01

    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). 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. 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). 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.

  12. Factors affecting the efficiency of aerosol therapy with pressurised metered-dose inhalers through plastic spacers.

    PubMed

    Chuffart, A A; Sennhauser, F H; Wildhaber, J H

    2001-01-12

    The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler (pMDI) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers. In addition, we aimed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination. Particle size distribution and output from salbutamol pMDIs containing either CFC propellants (Ventolin) or HFA propellants (Airomir) were measured using a multistage liquid impinger (MSLI) and compared to that through both detergent-coated (non-static) or untreated (static) large volume (Nebuhaler, Volumatic) and small volume (Aerochamber) plastic spacers. Flow-volume curves (FEV1) were obtained from twelve asthmatic children with known significant bronchodilator response (8 males), aged 13-17 years, randomly inhaling salbutamol from a CFC-pMDI through a static spacer (Nebuhaler) and from an HFA-pMDI through a non-static spacer (Nebuhaler). In vitro output of particles in the respirable range (< 6.8 microns) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers. Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17-82%. The mean (SD) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1% (6.3%) compared to 17.5% (7.9%) after inhalation from an HFA-pMDI through a non-static spacer (p = 0.002). Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI. However, electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers, and can be reduced by soaking the spacer in a household detergent. Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response.

  13. Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma.

    PubMed Central

    Selroos, O.; Löfroos, A. B.; Pietinalho, A.; Riska, H.

    1994-01-01

    BACKGROUND--Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients. METHODS--Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler). RESULTS--Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%). CONCLUSIONS--Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown. PMID:7878558

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

    PubMed

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

    2015-01-01

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

  15. Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat Soft Mist Inhaler vs. a conventional metered dose inhaler plus spacer in children with asthma.

    PubMed

    von Berg, Andrea; Jeena, Prakash M; Soemantri, Peter A; Vertruyen, André; Schmidt, Peter; Gerken, Fronke; Razzouk, Hassan

    2004-03-01

    The objective of this study was to compare the efficacy and safety of ipratropium bromide/fenoterol hydrobromide (IB/FEN; Berodual) delivered from the novel propellant-free Respimat Soft Mist Inhaler (SMI) with that from a chlorofluorocarbon (CFC) metered-dose inhaler (MDI) plus spacer in children with asthma. The study followed a multicenter, randomized, double-blind (within Respimat SMI), parallel-group design. During the 2-week run-in period, patients received two actuations of CFC-MDI tid (IB 20 microg/FEN 50 microg per actuation) via a spacer (Aerochamber) (MDI 40/100). Patients (n=535) were then randomized to: Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB 20 microg/FEN 50 microg (Respimat SMI 20/50), one actuation tid or CFC-MDI containing IB 20 microg/FEN 50 microg per actuation (in total 1B 40 microg/FEN 100 microg), or two actuations tid via Aerochamber (MDI 40/100), for 4 weeks. The primary endpoint was the change in forced expiratory volume in 1 second (FEV1) during the first 60 min after dosing (area under the curve from 0-1 h [AUC(0-1 h)]) on day 29. Analysis of the primary endpoint demonstrated that the efficacy of Respimat SMI 10/25 and 20/50 was equivalent to or greater than that of MDI 40/100. Similar results indicating that Respimat SMI 10/25 and 20/50 were not inferior to MDI 40/100 were also found on days 1 and 15. Analyses of other secondary endpoints supported these results. The safety profile of Respimat SMI was comparable to that of the CFC-MDI plus spacer. In conclusion, IB/FEN delivered via Respimat SMI is at least as effective as, and is as safe as, when delivered via CFC-MDI plus Aerochamber in children with asthma. Use of Respimat SMI thus enables a 2-4-fold reduction in the nominal dose of IB/FEN, and obviates the need for a spacer. Copyright 2004 Wiley-Liss, Inc.

  16. The formulation of a pressurized metered dose inhaler containing theophylline for inhalation.

    PubMed

    Zhu, Bing; Haghi, Mehra; Goud, Mary; Young, Paul M; Traini, Daniela

    2015-08-30

    Theophylline (TP) is a bronchodilator used orally to treat chronic obstructive pulmonary disease (COPD) that has been associated with multiple side effects, tempering its present use. This study aims to improve COPD treatment by creating a low-dose pressurized metered dose inhaler (pMDI) inhalable formulation of TP. Aerosol performance was assessed using Andersen Cascade Impaction (ACI). Solubility of TP in HFA 134/ethanol mixture was measured and morphology of the particles analyzed with a scanning electron microscope (SEM). Calu-3 cell viability, epithelial cell transport and inflammatory-response assays were conducted to study the impact of the formulation on lung epithelial cells. The mass deposition profile of the formulation showed an emitted dose of 250.04±14.48μg per 5 actuations, achieving the designed nominal dose (50μg/dose). SEM showed that the emitted particles were hollow with spherical morphology. Approximately 98% of TP was transported across Calu-3 epithelial cells and the concentration of interleukin-8 secreted from Calu-3 cells following stimulation with tissue necrosis factor-α (TNF-α) resulted in significantly lower level of interleukin-8 released from the cells pre-treated with TP (1.92±0.77ng·ml(-1) TP treated vs. 8.83±2.05ng·ml(-1) TNF-α stimulated, respectively). The solution pMDI formulation of TP developed in present study was shown to be suitable for inhalation and demonstrated anti-inflammatory effects at low doses in Calu-3 cell model. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Baseline Symptom Score Impact on Benefits of Glycopyrrolate/Formoterol Metered Dose Inhaler in COPD.

    PubMed

    Martinez, Fernando J; Fabbri, Leonardo M; Ferguson, Gary T; Orevillo, Chad; Darken, Patrick; Martin, Ubaldo J; Reisner, Colin

    2017-07-16

    The clinical severity of COPD is currently categorized by symptom burden and exacerbation risk. Previous 24-week phase III trials (NCT01854645 and NCT01854658) that demonstrated better improvement of lung function with glycopyrrolate/formoterol fumarate (GFF) metered dose inhaler (MDI) (an MDI fixed-dose of GFF 18/9.6 μg) over individual monocomponent MDIs included a cross-section of patients with moderate to very severe airflow limitation and a broad range of COPD symptoms. These post hoc analyses of pooled data investigated whether baseline symptom burden, assessed using the COPD Assessment Test (CAT) score, impacted GFF MDI-associated improvements in lung function, health status, rescue medication use, and exacerbation risk. In 3,699 patients, improvement in FEV1 at week 24 between the GFF MDI and monocomponent MDIs and a placebo MDI was similar in magnitude regardless of baseline CAT score. In contrast, the magnitude of mean difference in the St. George's Respiratory Questionnaire total score for GFF MDI vs monocomponent MDIs and the placebo MDI increased with increasing baseline CAT scores. Likewise, reduced rescue medication use and lower exacerbation risk were more pronounced in GFF MDI groups with a higher baseline symptom burden. Beneficial effects of GFF MDI on health status, rescue medication use, and exacerbation risk in symptomatic patients with COPD increased as a function of baseline symptom burden, whereas lung function benefits were independent. These data suggest a greater clinical benefit from dual bronchodilators in symptomatic patients than in patients without symptoms. ClinicalTrials.gov; No.: NCT01854645 and NCT01854658; URL: www.clinicaltrials.gov. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. 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.

  19. Nebulizers or pressurized metered-dose inhalers in the treatment of asthma exacerbations.

    PubMed

    Radzik, Daniele; Peroni, Diego G; Pescollderungg, Lydia; Piacentini, Giorgio L; Chatzimichail, Atanasio; Boner, Attilio L

    2005-01-01

    The use of inhaled beta2-agonists delivered by a metered-dose inhaler (MDI) with a holding chamber (spacer) actually is considered the best treatment for childhood acute asthma. However, its use in daily practice still seems rather limited. The aim of this study was to investigate, using a questionnaire, the use of a nebulizer or MDI as the first-line method for delivering inhaled beta2-agonists in children with acute asthma. A questionnaire was developed and distributed to 22 pediatric departments and to 131 family pediatricians (FPs) in northeast Italy. We showed that in the hospitals the episodes of acute asthma usually were treated with bronchodilators administered by wet nebulization (95.45%). This was the case also for FPs (70.9%). However, 29.1% of FPs usually advised the use of an MDI/holding chamber to children with acute asthma. Despite the established efficacy of inhaled beta2-agonists administrated with an MDI compared with wet nebulization in acute asthma, this practice still is rather limited. The use of wet nebulization was more evident in hospital settings compared with community medicine. Emergency room visits may represent a missed opportunity to promote an effective method of delivering bronchodilators in childhood asthma.

  20. Use of pressurized metered dose inhalers in patients with chronic obstructive pulmonary disease: review of evidence.

    PubMed

    Aggarwal, Bhumika; Gogtay, Jaideep

    2014-06-01

    The inhaled route is considered to be the best route to administer drugs for treating respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD), for both safety and efficacy. Inhalation devices are classified into four types - pressuriszed metered dose inhalers (pMDIs), dry powder inhalers, breath actuated inhalers and nebulizers. pMDIs are portable, convenient, multi-dose devices and these advantages have made them very popular with patients. They were introduced in the 1950s as the first portable, multi-dose delivery system for bronchodilators. Even though pMDIs are the most widely used devices for inhalation therapy in asthma and COPD, studies establishing their use and providing clinical data with bronchodilators and combination therapies in patients with COPD are limited. A summary of the use of pMDI with spacers in patients with COPD in terms of lung deposition and impact on lung function are presented in this review article. A review of use of the pMDI device in patients with COPD with different available and prescribed medications (bronchodilators-β2-agonists and anticholinergics, and their combination with inhaled corticosteroids) is discussed.

  1. Comparison of the systemic pharmacodynamic effects and pharmacokinetics of salmeterol delivered by CFC propellant and non-CFC propellant metered dose inhalers in healthy subjects.

    PubMed

    Kempsford, Rodger; Handel, Malcolm; Mehta, Rashmi; De Silva, Mariza; Daley-Yates, Peter

    2005-04-01

    This was a randomised, double-blind, placebo-controlled, cross-over study comparing the systemic pharmacodynamic effects (heart rate and serum potassium) and pharmacokinetics of salmeterol delivered by the non-CFC hydrofluoralkane (HFA) propellant 134a and the CFC propellant (propellant 11/12) metered dose inhalers (MDI) in healthy subjects. At the therapeutic dose (50 microg), salmeterol-mediated systemic pharmacodynamics were equivalent for the HFA and CFC MDIs. Higher doses of salmeterol (150 and 300 microg) produced dose-related beta-agonist pharmacodynamic effects irrespective of the propellant. However, these effects were lower with salmeterol HFA MDI than with the salmeterol CFC MDI at all dose levels. Overall, salmeterol Cmax and AUC(0-t) values were lower for salmeterol HFA compared with salmeterol CFC MDI. At the highest dose (300 microg), where a full pharmacokinetic profile was obtained, exposure to salmeterol delivered by the HFA MDI compared with the salmeterol CFC MDI was 27% and 30% lower for Cmax and AUC(0-t), respectively. Maximum plasma concentrations were generally seen in the first plasma samples taken 5 min after the start of dosing. Salmeterol HFA was well-tolerated. At supratherapeutic doses, adverse events were typical for high-dose salmeterol with fewer adverse events occurring with the HFA compared with the CFC formulation. These data indicate that the salmeterol HFA MDI would not be associated with a significantly different pharmacodynamic, safety and tolerability profile compared with the salmeterol CFC MDI.

  2. A Randomized Controlled Trial of 2 Inhalation Methods When Using a Pressurized Metered Dose Inhaler With Valved Holding Chamber.

    PubMed

    Stephen, Divya; Vatsa, Manju; Lodha, Rakesh; Kabra, S K

    2015-12-01

    Information on the comparative efficacy of single deep breathing versus tidal breathing for inhaled asthma medications is limited, although such information can be of much use for the treatment of patients suffering from asthma. The objective of the present study was to compare the relative difference in improvement in peak expiratory flow (PEF) with single maximal inhalation with breath-holding versus 5 tidal breaths during inhalation of salbutamol from a pressurized metered dose inhaler (pMDI) with valved holding chamber (VHC) in children 5-15 y of age with asthma. The randomized controlled trial was carried out on children with asthma between 5 and 15 y of age using a pMDI with a VHC either by a single deep breath with breath-hold or 5 tidal breaths. The experimental group received 200 μg of salbutamol from the pMDI with VHC with a single maximal inhalation and breath-hold technique, whereas the control group received 200 μg of salbutamol from pMDI with VHC using the 5 tidal breaths technique. The outcome variable, PEF, was reassessed 30 min after salbutamol use. Eighty-two subjects (mean age 8.79 ± 2.5 y, 65 boys and 17 girls) were analyzed. There was significant improvement in the PEF, from baseline (pre-intervention) to post-intervention within the single maximal inhalation with breath-hold group and tidal breathing group independently (P < .001). The mean difference in improvement in PEF between the single maximal inhalation with a breath-hold and 5 tidal breaths group was 30.0 ± 18.16 and 28.29 ± 13.94 L/min, respectively, and was not statistically significant (P = .88). Single maximal inhalation with a breath-hold technique is not superior to tidal breathing for improvement in PEF following salbutamol inhalation. Either method may be used in children between 5 and 15 y of age. (India's Clinical Trials Registry CTRI/2013/04/003559.). Copyright © 2015 by Daedalus Enterprises.

  3. Asthma pressurised metered dose inhaler performance: propellant effect studies in delivery systems.

    PubMed

    Sellers, William F S

    2017-01-01

    Current pressurised metered dose asthma inhaler (pMDI) propellants are not inert pharmacologically as were previous chlorofluorocarbons, have smooth muscle relaxant' partial pressure effects in the lungs and inhaled hydrofluoroalkane 134a (norflurane) has anaesthetic effects. Volumes of propellant gas per actuation have never been measured. In-vitro studies measured gas volumes produced by pMDIs on air oxygen (O2) levels in valved holding chambers (VHC) and the falls in O2% following actuation into lung ventilator delivery devices. Volumes of propellant gas hydrofluoroalkane (HFA) 134a and 227ea and redundant chlorofluorocarbons (CFC) varied from 7 ml per actuation from a small salbutamol HFA inhaler to 16 ml from the larger. Similar-sized CFC pMDI volumes were 15.6 and 20.4 ml. Each HFA salbutamol inhaler has 220 full volume discharges; total volume of gas from a small 134a pMDI was 1640 ml, and large 3885 ml. Sensing the presence of liquid propellant by shaking was felt at the 220th discharge in both large and small inhalers. Because of a partial pressure effect, VHC O2% in air was reduced to 11% in the smallest 127 ml volume VHC following 10 actuations of a large 134a salbutamol inhaler. The four ventilator delivery devices studied lowered 100% oxygen levels to a range of 93 to 81% after five actuations, depending on the device and type of pMDI used. Pressurised inhaler propellants require further study to assess smooth muscle relaxing properties.

  4. Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

    PubMed

    Goldberg, J; Freund, E; Beckers, B; Hinzmann, R

    2001-02-01

    Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.

  5. Metered dose inhaler-spacer use education effects on achieve asthma control in children.

    PubMed

    Türkeli, Ahmet; Yılmaz, Özge; Yüksel, Hasan

    2016-06-01

    Improper Metered Dose Inhaler (MDI)-spacer use technique can result in less than optimal delivery of medicine to the lungs and poor asthma outcomes. The aim of this study was to evaluate the influence of standardized education on proper MDI- spacer use and asthma control in children with asthma and to identify the factors associated with these results. This is a cohort study that evaluated the influence of standardized education about MDI-Spacer device use on asthma control in children. Asthmatic children using MDI-Spacer device and their parents were enrolled in this study. Children were followed up for two months after standardized education and the change in asthma control was recorded. Thirty eight children (14 females and 24 males) aged between 2.5 and 13 years were enrolled in the study. Mean age of the children was 7.5 ± 2.8 years. Six patients were lost to follow up and thirty two patients completed the study. Mean inhalation technique score was 4.9 ± 1.3 before education and increased significantly to 7.8 ± 0.4 after education (p< 0.001). Mean Asthma Control Questionnaire (ACQ) score decreased significantly with education (0.77 ± 0.9 vs 0.1 ± 0.1 respectively, p< 0.001). Similarly, mean asthma symptom score (ASS) decreased significantly from 4.3 ± 3.6 to 0.2 ± 0.7 with education (p< 0.001). Most common mistake in use of MDI-Spacer device use was detected to be lack of mouth rinsing after use before education in 78.9% of the patients. Providing standardized education about MDI-Spacer device use to children and parents leads to correct MDI-Spacer device use and is associated with improvement in asthma symptom score and asthma control.

  6. Albuterol delivery in a neonatal ventilated lung model: Nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers.

    PubMed

    Lugo, R A; Kenney, J K; Keenan, J; Salyer, J W; Ballard, J; Ward, R M

    2001-03-01

    The aim of this study was to compare albuterol delivery in a neonatal ventilated lung model, using three delivery methods: 1) jet nebulizer; 2) chlorofluorocarbon-pressurized metered dose inhaler (CFC-MDI) actuated into an ACE(R) spacer; and 3) hydrofluoroalkane-pressurized MDI (HFA-MDI) actuated into an ACE(R) spacer. The bench model consisted of a mechanically ventilated infant test lung with ventilator settings to simulate a very low birth weight neonate with moderate lung disease. Albuterol solution (0.5%) was nebulized at the humidifier and temperature port, 125 cm and 30 cm from the Y-piece, respectively. Albuterol metered dose inhalers (MDIs) were actuated into an ACE(R) spacer that was tested in two positions: 1) inline between the endotracheal (ET) tube and the Y-piece; and 2) attached to the ET tube and administered by manual ventilation. Albuterol was collected on a filter at the distal end of the ET tube and was quantitatively analyzed by high performance liquid chromatography. Albuterol delivery by CFC-MDI (position 1, 4.8 +/- 1.0%, vs. position 2, 3.8 +/- 1.6%, P > 0.05) and HFA-MDI (position 1, 5.7 +/- 1.6%, vs. position 2, 5.5 +/- 2.4%, P > 0.05) were significantly greater than delivery by nebulization at 30 cm (0.16 +/- 0.07%) and 125 cm (0.15 +/- 0.03%) from the Y-piece (P < 0.001). A single actuation of albuterol MDI delivered the equivalent of nebulizing 2.5-3.7 mg of albuterol solution. We conclude that albuterol administered by MDI and ACE(R) spacer resulted in more efficient delivery than by nebulization in this mechanically ventilated neonatal lung model. There was no significant difference in drug delivery between CFC-MDI and HFA-MDI; nor did the placement of the spacer significantly affect drug delivery.

  7. The efficacy of metered-dose inhalers with a spacer device in the pediatric setting.

    PubMed

    Buxton, Lance J; Baldwin, Joan H; Berry, Judith A; Mandleco, Barbara L

    2002-09-01

    To systematically review the published research and report on the efficacy of using a metered-dose inhaler with a spacer (MDI-S) device in a pediatric setting to treat acute exacerbations of asthma. A literature search was conducted on the CINAHL, Medline, and Cochrane databases; additional searches were made by hand from the reference lists in each study retrieved from databases and from review articles written on the same topic. This critical appraisal of the research demonstrates the MDI-S is as effective as the nebulizer, faster in the delivery of medication, and cost-effective. No significant difference between the MDI-S and nebulizer in delivering medication in an acute exacerbation of asthma was found in this analysis. The practitioner's choice of delivery methods should reflect the family's preference, the practice situation, and economic considerations.

  8. Current Inhalers Deliver Very Small Doses to the Lower Tracheobronchial Airways: Assessment of Healthy and Constricted Lungs

    PubMed Central

    Walenga, Ross L.; Longest, P. Worth

    2015-01-01

    To evaluate the regional delivery of conventional aerosol medications, a new whole-lung computational fluid dynamics (CFD) modeling approach was applied for metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols delivered to healthy and constricted airways. The CFD approach included complete airways through the third respiratory bifurcation (B3) and applied the new stochastic individual pathway (SIP) modeling technique beyond B3 through the remainder of the conducting airways together with a new model of deposition in the alveolar region. Bronchiolar (B8-B15) deposition fraction (DF) values were low (~1%) for both MDI and DPI aerosols with the healthy geometry, while delivery to the constricted model was even lower, with DF values of 0.89% and 0.81% for the MDI and DPI, respectively. Calculating dose per unit-surface-area for the commercial MDI and DPI products resulted in approximately 10−3 μg/cm2 in the lower tracheobronchial (TB) region of B8-B15 and 10−4 μg/cm2 in the alveolar region. Across the lung, dose per unit-surface-area varied by 2 orders of magnitude, which increased to 4 orders of magnitude when the mouth-throat region was included. The MDI and DPI both provided very low drug dose per unit-surface-area to the small TB and alveolar airways. PMID:26852850

  9. Current Inhalers Deliver Very Small Doses to the Lower Tracheobronchial Airways: Assessment of Healthy and Constricted Lungs.

    PubMed

    Walenga, Ross L; Longest, P Worth

    2016-01-01

    To evaluate the regional delivery of conventional aerosol medications, a new whole-lung computational fluid dynamics modeling approach was applied for metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols delivered to healthy and constricted airways. The computational fluid dynamics approach included complete airways through the third respiratory bifurcation (B3) and applied the new stochastic individual pathway modeling technique beyond B3 through the remainder of the conducting airways together with a new model of deposition in the alveolar region. Bronchiolar (B8-B15) deposition fraction values were low (∼1%) for both MDI and DPI aerosols with the healthy geometry, whereas delivery to the constricted model was even lower, with deposition fraction values of 0.89% and 0.81% for the MDI and DPI, respectively. Calculating dose per unit surface area for the commercial MDI and DPI products resulted in approximately 10(-3) μg/cm(2) in the lower tracheobronchial region of B8-B15 and 10(-4) μg/cm(2) in the alveolar region. Across the lung, dose per unit surface area varied by 2 orders of magnitude, which increased to 4 orders of magnitude when the mouth-throat region was included. The MDI and DPI both provided very low drug dose per unit surface area to the small tracheobronchial and alveolar airways.

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

    PubMed

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

    1999-05-01

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

  11. Barriers to metered-dose inhaler/spacer use in Canadian pediatric emergency departments: a national survey.

    PubMed

    Osmond, Martin H; Gazarian, Madlen; Henry, Richard L; Clifford, Tammy J; Tetzlaff, Jennifer

    2007-11-01

    Metered-dose inhalers and spacers (MDI+S) are at least as effective as nebulizers for treating children with mild to moderate asthma exacerbations. Despite advantages in terms of efficacy, side effects, and ease of use, MDI+S are not used in many North American pediatric emergency departments (PEDs). To survey emergency physicians, emergency nurses, and respirologists in Canadian pediatric teaching hospitals regarding their practices, beliefs, and barriers to change with respect to bronchodilator delivery. This was a cross-sectional, mailed survey of all emergency physicians, all respirologists, and a random sample of emergency nurses at ten Canadian PEDs. A total of 291 of 349 health care professionals (83%) responded. Twenty-one percent of emergency physicians use MDI+S in the PED (largely concentrated at two "user sites"). A majority at nonuser sites, and virtually all professionals at user sites, responded that MDI+S are at least as effective as nebulizers, switching to MDI+S is justified by existing research, patient outcomes would be equal or better, and they have the required knowledge and skills to use MDI+S in the emergency department. The largest perceived barriers to MDI+S implementation include concerns regarding safety and costs, related to feasibility of providing and sterilizing spacers, and parental expectations for nebulizers. Other barriers included staff beliefs regarding the effectiveness of MDI+S, changes in nursing workload, and lack of a physician champion for change. MDI+S are infrequently used to treat patients with acute asthma in Canadian PEDs, despite the fact that most emergency staff believe they are effective. Important barriers to using MDI+S have been identified in this study and should be used to guide future implementation strategies.

  12. Results of a programme to improve house staff use of metered dose inhalers and spacers.

    PubMed

    Lee-Wong, M; Mayo, P H

    2003-04-01

    Metered dose inhalers (MDIs) and spacers are used widely in the treatment of asthma. Medical personnel who are responsible for training patients must themselves be proficient with the devices. The proficiency of a group of new medical interns with use of MDI and spacer devices was determined, and improvement in their use of these devices was sought. Fifty six medical interns tested at the start of their first house staff training year. The ability of medical interns to use MDIs and spacers was assessed using a visual scoring system before and after a large group lecture emphasising proper device use and once again after an intensive one-on-one training session with an attending physician. Initially, only 5% used an MDI perfectly. This improved to 13% after a lecture and demonstration, and 73% after an intensive one-on-one session. Almost no new interns could use a collapsible or tube spacer properly initially. This improved to 15% and 29% respectively after a lecture. After one-on-one training, correct technique was increased to 69% for collapsible spacer and 95% for the tube spacer. Analysis of individual steps of MDI use showed that interns had particular difficulty in coordinating actuation with inhalation. The tube spacer appeared easiest to learn. Incoming medical house staff have limited ability to use MDI with and without spacers. A large group lecture is relatively ineffective when compared with a one-on-one training session in training with these devices.

  13. Pressurised metered dose inhaler-spacer technique in young children improves with video instruction.

    PubMed

    Shaw, Nicole; Le Souëf, Peter; Turkovic, Lidija; McCahon, Lucy; Kicic, Anthony; Sly, Peter D; Devadason, Sunalene; Schultz, André

    2016-07-01

    The importance of good device technique to maximise delivery of aerosolised medications is widely recognised. Pressurised metered dose inhaler (pMDI)-spacer technique was investigated in 122 children, aged 2-7 years, with asthma. Eight individual steps of device technique were evaluated before and after viewing an instructional video for correct device technique. Video measurements were repeated every three months for nine months. Device technique improved directly after video instruction at the baseline study visit (p < 0.001) but had no immediate effect at subsequent visits. Additionally, pMDI-spacer technique improved with successive visits over one year for the group overall as evidenced by increases in the proportion of children scoring maximal (p = 0.02) and near-maximal (p = 0.04) scores. Repeated video instruction over time improves inhaler technique in young children. • Correct device technique is considered essential for sufficient delivery of inhaled medication. • Poor inhaler use is common in young asthmatic children using pressurised metered dose inhalers and spacers. What is New: • Video instruction could be used as a strategy to improve device technique in young children.

  14. The chlorofluorocarbon to hydrofluoroalkane transition: the effect on pressurized metered dose inhaler suspension stability.

    PubMed

    Brindley, A

    1999-12-01

    The phase out of chlorofluorocarbon (CFC) propellants has necessitated the reformulation of pressurized metered dose inhalers (pMDIs) with hydrofluoroalkane (HFA) propellants. One of the main challenges has been that conventional surfactants used for CFC-based pMDIs were not soluble in HFAs. Since one of the main aims of a pMDI is to deliver a reproducible dose of medication to the patient, it is vital that, for suspension-type pMDI formulations, the suspension is stabilized sufficiently for a reproducible dose to be delivered. A new technique has been developed that measures suspension stability more objectively than before. This technique, optical suspension characterization, was used to compare the performance of different formulations of respiratory drugs in HFAs. The optical suspension characterization data were correlated with conventional analytic techniques for the determination of the stability of the suspension formulation.

  15. Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology.

    PubMed

    Kleinstreuer, Clement; Shi, Huawei; Zhang, Zhe

    2007-01-01

    The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the

  16. Metered dose inhaler with spacer versus dry powder inhaler for delivery of salbutamol in acute exacerbations of asthma: a randomized controlled trial.

    PubMed

    Lodha, Rakesh; Gupta, Gaurav; Baruah, Bedanta Prakash; Nagpal, Rajiv; Kabra, S K

    2004-01-01

    Delivery of various drugs by aerosol inhalation is the mainstay of treatment of asthma. Many delivery systems have been developed for children, each having its own advantages and disadvantages. Studies comparing the clinical efficacy of metered dose inhalers (MDI) and dry powder inhalers (DPI) in the treatment of acute exacerbations of asthma in children are limited. We conducted a study to compare the response to salbutamol inhalation delivered by metered dose inhaler with a spacer versus rotahaler (DPI) in children presenting with mild or moderate acute exacerbations of asthma. Children in the age group of 5-15 years who presented with a mild or moderate acute exacerbation of asthma were randomized to receive 400 micrograms salbutamol by either a MDI with spacer or a DPI. The changes in the wheezing and accessory muscle scores, SaO2, and PEFR were recorded and subjected to statistical tests for significance. One hundred and fifty three children were studied; 78 were assigned to the MDI-spacer group and 75 to rotahaler (DPI) group. After receiving treatment, the PEFR improved by about 11% in both the groups. The oxygen saturation increased by 2% in both the groups. Within each group, the improvement in PEFR, SaO2, wheeze and accessory muscle score after the treatment was statistically significant. In both the groups the children co-operated equally well. Metered dose inhaler with spacer and dry powder inhaler have equal efficacy in delivering salbutamol in therapy of mild to moderate acute exacerbations of bronchial asthma in children between 5-15 years of age.

  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. Effects of salbutamol given by metered-dose inhaler on dispersion of ventricular repolarization.

    PubMed

    Polat, Tuğçin Bora; Saz, Eylem Ulaş; Nursoy, Mustafa Atilla

    2011-05-01

    Salbutamol has previously been shown to increase the QT dispersion (QTd), which may be associated with high risk of cardiac arrhythmia in asthmatics. Cardiac effects of salbutamol occur in dose-related manner and salbutamol dose given by metered-dose inhaler (MDI) during acute asthma attack is commonly lower than the dose given by nebulizer. This prospective cohort study aimed to assess the effect of salbutamol given by MDI on QTd in the course of moderate acute asthma attack. Thirty-two children, between 5-15 years of age, who were able to perform spirometric maneuvers and salbutamol administration by MDI through the spacer, were enrolled. Salbutamol was administered at a dose of 50 µg/kg three times at 15-20 minute intervals. Clinical features, spirometric parameters and QT measurements from the standard electrocardiograms were studied at baseline and 15 minute after the third inhalation of salbutamol. The relation between the continuous variables was evaluated by using paired Student's t-test. Overall, treatments were well-tolerated, significant improvement of pulmonary index scores and spirometric parameters were observed after treatment. No significant difference was observed between the pre and post-treatment values in QTd (30.4±5.6 ms; 33.7±6.2 ms, p=0.086) and corrected QTd (38.8±6.4 ms; 40.7±7.7 ms, p=0.18). Salbutamol administered using metered dose inhaler showed satisfying clinical improvement with notably lower doses than the dose given by nebulizer and does not affect ventricular repolarization in children with moderate acute asthmatic attack.

  19. Scintigraphic Assessment of Deposition of Radiolabeled Fluticasone Delivered from a Nebulizer and Metered Dose Inhaler in 10 Healthy Dogs.

    PubMed

    Chow, K E; Tyrrell, D; Yang, M; Abraham, L A; Anderson, G A; Mansfield, C S

    2017-09-29

    Aerosolized medications increasingly being are used to treat respiratory diseases in dogs. No previous studies assessing respiratory tract deposition of radiolabeled aerosols have been performed in conscious dogs. Assess respiratory tract deposition of radiolabeled, inhalant corticosteroid (fluticasone propionate labeled with (99m) Tc) delivered from a nebulizer and metered dose inhaler (MDI) to healthy dogs. Ten healthy Foxhounds. Prospective, randomized, cross-over pilot study. Initial inhalation method (nebulizer or MDI) was randomly assigned. Treatments were crossed over after a 7-day washout period. Treatments initially were performed using sedation. Dogs were imaged using 2-dimensional planar scintigraphy, with respiratory tract deposition quantified by manual region-of-interest analysis. Deposition calculated as percentage of delivered dose. Six of 10 dogs were randomly selected and reassessed without sedation. Inhalation method had significant effect on respiratory tract deposition (P = 0.027). Higher deposition was achieved by nebulization with mean deposition of 4.2% (standard deviation [SD], 1.4%; range, 1.9-6.1%); whereas MDI treatment achieved a mean of 2.3% (SD, 1.4%; range, 0.2-4.2%). Nebulization achieved higher respiratory tract deposition than MDI in 7 of 10 dogs. No statistical difference (P = 0.68) was found between mean respiratory tract deposition achieved in dogs when unsedated (3.8%; SD, 1.5%) or sedated (3.6%; SD, 1.7%). Study confirms respiratory tract deposition of inhalant medications delivered from a nebulizer and MDI in healthy dogs, breathing tidally with and without sedation. Respiratory tract deposition in these dogs was low compared to reported deposition in adult humans, but similar to reported deposition in children. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. Randomized comparison of a dry powder inhaler and metered dose inhaler with spacer in management of children with asthma.

    PubMed

    Singh, M; Kumar, L

    2001-01-01

    Comparison of the clinical efficacy of a transparent, DPI (transparent Rotahaler) with MDI and spacers in childhood asthma. Open, randomized, crossover trial. Out patient clinic of a referral pediatric center. Thirty (mean 6.1 +/-2.7 years) children with moderate persistent asthma were randomized to receive long-term medications by a DPI or a metered dose inhaler with spacer for six weeks and then crossed over to receive the same drugs for another period of six weeks after an initial run in period of one week for training in inhalation techniques. The preventative therapy consisted of inhaled Beclomethasone dipropionate (600 mcg/day) and Salbutamol as per requirement. The patients were monitored by a symptom diary, weekly PEFR, and PEFR variability by the parental record of PEFR measurements at home with Mini Wright s Peakflow meter in accordance with the Consensus guidelines. Comparisons made on weekly symptom scores, PEFR at interval visits, PEFR variability, additional beta sympathomimetic use and acute exacerbations of asthma did not reveal any statistically significant differences during the two treatment periods (>0.05). Metered dose inhaler and dry powder inhaler have equal efficacy in anti-inflammatory therapy of bronchial asthma in children.

  1. An evaluation of impact of educational interventions on the technique of use of metered-dose inhaler by patients.

    PubMed

    Purohit, Avadhi Nirajkumar; Patel, P P; Gandhi, A M; Desai, M K

    2017-01-01

    The objective of this study is to evaluate the impact of two educational interventions that are demonstration versus pictorial Leaflet in patients using metered-dose inhaler (MDI). This interventional study was done in patients who were prescribed drugs through MDI at Tuberculosis and Chest Department. The patients were enrolled in Group A or Group B as per random number table method. The method of use of MDI was assessed using a checklist based on the technique described in the WHO Guide to good prescribing. Patients in Group A were taught the use of MDI by demonstration of the technique by the investigator. Patients in Group B were educated about the technique by a pictorial leaflet based on the technique. Patients were followed up after 15 days and assessed for correct technique for use of the MDI. A total 100 patients were included in the study and were allotted to Group A (47) and Group B (53). Ninety-five percent of the patients had been taught by the treating physician about the method of use of MDI. All the patients at the baseline placed the lips tightly around the mouthpiece and held the aerosol as indicated in the manufacturer's instructions while the step least followed was coughing up the sputum before inhalation. The average steps correctly followed by the patients in Group A and B at baseline were 5.17 ± 2.07 and 5.11 ± 2.04, respectively. These improved significantly to 9.19 ± 0.67 and 6.67 ± 0.63 in Group A and B, respectively, postintervention. The five essential steps of using MDI were followed by 25.53% and 26.41% patients preintervention. An improvement in the technique of use of MDI was observed in 85.11% and 49.06% patients (P = 0.003) postintervention. All the ten steps of the technique were followed by 34.04% patients from Group A and none from Group B at postintervention evaluation (P = 0.0001). The inhalation technique for the use of MDI used by the patients is inappropriate. Educational interventions such as demonstration or

  2. An evaluation of impact of educational interventions on the technique of use of metered-dose inhaler by patients

    PubMed Central

    Purohit, Avadhi Nirajkumar; Patel, P. P.; Gandhi, A. M.; Desai, M. K.

    2017-01-01

    OBJECTIVES: The objective of this study is to evaluate the impact of two educational interventions that are demonstration versus pictorial Leaflet in patients using metered-dose inhaler (MDI). MATERIALS AND METHODS: This interventional study was done in patients who were prescribed drugs through MDI at Tuberculosis and Chest Department. The patients were enrolled in Group A or Group B as per random number table method. The method of use of MDI was assessed using a checklist based on the technique described in the WHO Guide to good prescribing. Patients in Group A were taught the use of MDI by demonstration of the technique by the investigator. Patients in Group B were educated about the technique by a pictorial leaflet based on the technique. Patients were followed up after 15 days and assessed for correct technique for use of the MDI. RESULTS: A total 100 patients were included in the study and were allotted to Group A (47) and Group B (53). Ninety-five percent of the patients had been taught by the treating physician about the method of use of MDI. All the patients at the baseline placed the lips tightly around the mouthpiece and held the aerosol as indicated in the manufacturer's instructions while the step least followed was coughing up the sputum before inhalation. The average steps correctly followed by the patients in Group A and B at baseline were 5.17 ± 2.07 and 5.11 ± 2.04, respectively. These improved significantly to 9.19 ± 0.67 and 6.67 ± 0.63 in Group A and B, respectively, postintervention. The five essential steps of using MDI were followed by 25.53% and 26.41% patients preintervention. An improvement in the technique of use of MDI was observed in 85.11% and 49.06% patients (P = 0.003) postintervention. All the ten steps of the technique were followed by 34.04% patients from Group A and none from Group B at postintervention evaluation (P = 0.0001). CONCLUSION: The inhalation technique for the use of MDI used by the patients is inappropriate

  3. From hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIs.

    PubMed

    Kunka, R; Andrews, S; Pimazzoni, M; Callejas, S; Ziviani, L; Squassante, L; Daley-Yates, P T

    2000-06-01

    Fluticasone propionate pressurized metered dose inhalers (pMDIs) containing the hydrofluoroalkane (HFA) propellant, HFA 134a, are being developed to replace existing chlorofluorocarbon (CFC) pMDIs. This is part of the ongoing worldwide project to limit the damage to the earth's ozone layer. The in vivo performance and dose proportionality of fluticasone propionate HFA 134a pMDIs was examined for fluticasone propionate doses of 400, 1000 and 2000 microg using the 50, 125 and 250 microg strength pMDIs, respectively. The 125 and 250 microg strength HFA 134a pMDIs were compared with corresponding fluticasone propionate CFC pMDIs. Twenty-three healthy subjects participated in this single dose, randomized, five-way, cross-over study. Serial blood samples were collected 24 h post-dose to measure fluticasone propionate plasma concentrations. Twenty-four hour urinary-free cortisol was also measured before and after dosing. A dose-proportional increase in plasma fluticasone propionate concentrations was observed with increasing dose for the HFA 134a pMDIs. This was associated with a dose-related decrease in urinary cortisol excretion. Similar or lower fluticasone propionate systemic exposure was observed with the HFA 134a pMDIs compared to the corresponding CFC inhalers. The differences in systemic exposure observed for the HFA 134a and CFC pMDIs were too small to produce a differential effect on urinary cortisol excretion. Since fluticasone propionate has negligible oral bioavailability, the systemic exposure, which arises only from pulmonary absorption, is a measure of lung deposition. There was a good correlation between the in vitro fine particle mass produced by the different strengths and types of pMDI and the systemic exposure to fluticasone propionate. Therefore, the fluticasone propionate HFA 134a pMDI is an acceptable pharmaceutical alternative to the current CFC pMDI, producing similar lung deposition and no increase in systemic exposure at microgram equivalent

  4. Efficacy of metered-dose inhalers for children with acute asthma exacerbations.

    PubMed

    Goh, Anne Eng Neo; Tang, Jenny Poh Lin; Ling, Ho; Hoe, Teoh Oon; Chong, Ng Kee; Moh, Chay Oh; Huak, Chan Yiong

    2011-05-01

    To compare the effectiveness of the administration of inhaled beta-agonists delivered via a metered-dose inhaler (MDI) with spacers--as part of an evidence-based asthma pathway developed to manage acute asthma exacerbations in children at the emergency room level and in inpatient management--against administration via nebulization. Case with historical control. KK Women's and Children's Hospital (Singapore). A total of 19,951 children (infants to older children) aged 18 years and younger who attended the emergency room for asthma exacerbations. Average length of stay, proportion admitted to high dependency or intensive care, proportion readmitted for unresolved symptoms within 72 hr, cost per patient and overall. There was no increase in the mean proportion of emergency room attendances admitted to inpatient care with use of an MDI (mean difference 0.97%, 95% CI: -1.6-3.5%, P = 0.447), nor of children admitted to intensive care (0.21 vs. 0.20 pre- and post-pathway, P = 0.827) or to high dependency units (2.21 vs. 1.37 pre- and post-pathway, P = 0.200) but a significant reduction in the within 72 hr re-attendance rate (mean difference 1.4%, 95% CI: 0.78-2.0%, P < 0.001) with use of an MDI. The average length and cost per patient for an inpatient stay for acute asthma exacerbations was reduced with use of an MDI. The use of an MDI with spacer as part of an evidence-based asthma pathway was effective in the management of acute asthma exacerbations in the emergency room setting and for inpatient management. Copyright © 2010 Wiley-Liss, Inc.

  5. Comparison of the safety of drug delivery via HFA- and CFC-metered dose inhalers in CAO.

    PubMed

    Huchon, G; Hofbauer, P; Cannizzaro, G; Iacono, P; Wald, F

    2000-04-01

    The objective of this study was to compare the long-term safety of a fixed combination of fenoterol hydrobromide (50 microg) and ipratropium bromide (20 microg) delivered using a metered dose inhaler (MDI) formulated with a non-chlorinated propellant, hydrofluoroalkanel34a (HFA-MDI), with delivery using the conventional chlorofluorocarbon propellant (CFC-MDI, Berodual/Bronchodual). The study was designed according to Safety Assessment of Marketed Medicines (SAMM) guidelines, to reflect as far as possible the use of MDls under normal prescribing conditions. Two thousand and twenty-seven patients with chronic airways obstruction (CAO) were enrolled from 99 centres in France, 95 centres in Germany and 24 centres in Italy. Following a 2-week run-in period, patients were randomized on a 2:1 basis (1,348 patients to HFA-MDI, 679 patients to CFC-MDI) to receive a flexible dose regimen of the combination (2 puffs, 2-4 times a day, as prescribed by the investigator) during a 12-week open label phase. The overall incidence of adverse events was comparable between both groups. In addition, the incidence of respiratory side effects was also similar, with CAO exacerbations or bronchitis the most frequently recorded events. The safety profile of the HFA formulation was comparable to those of the marketed CFC-MDIs used in Germany and France/Italy. No clinically significant differences were detected between HFA134a or CFC driven inhalers on the switch from CFC- to HFA-MDI (2 weeks before randomisation versus 2 weeks after randomization). There was a trend for taste complaints to be reported more frequently by patients in the HFA-MDI group (0.7% before randomization versus 3.4% after randomization). This, however, was an expected finding as the HFA134a formulation does have a different taste to the CFC formulation. No difference between formulations was observed in the incidences of coughing or paradoxical bronchospasm. The incidence of falls in FEV1 >15% within 15 min following

  6. Randomized study of the safety, pharmacokinetics, and bronchodilatory efficacy of a proprietary glycopyrronium metered-dose inhaler in study patients with chronic obstructive pulmonary disease

    PubMed Central

    2014-01-01

    Background Bronchodilator medications are central to the symptomatic management of chronic obstructive pulmonary disease (COPD). Metered-dose inhalers (MDIs) are the most commonly used devices to deliver treatment to patients with COPD and asthma, comprising approximately 70% of bronchodilator prescriptions. Proprietary porous-particle technology permits the formulation of long-acting muscarinic antagonists, long-acting β2-agonists, and a combination of both in hydrofluoroalkane (HFA) MDIs, providing a solution to formulation challenges inherent to the development of HFA MDIs, which have contributed to the development of dry-powder inhalers. Methods In this randomized, double-blind, 4-period, 6-treatment, placebo- and active-controlled, multicenter, crossover study, 4 ascending single doses of a proprietary glycopyrronium (GP) MDI were evaluated compared with Placebo MDI and open-label tiotropium (TIO) in study patients with COPD. Thirty-three study patients were enrolled and received single-dose administration of 4 of the 6 treatments (Placebo MDI, TIO 18 μg, or GP MDI at 14.4, 28.8, 57.6, and 115.2 μg ex-actuator) with an interval of 1 to 3 weeks between doses. The primary efficacy endpoint was peak change in forced expiratory volume in 1 second (FEV1). Results All 4 doses of GP MDI showed statistically superior efficacy compared with Placebo MDI for peak FEV1 (differences of 146 to 248 mL; P < .001), with a clear dose ordering of the response. Statistically significant differences compared with Placebo MDI were noted at almost all doses for the secondary FEV1 parameters (P ≤ .049) except 24-hour trough FEV1 at 28.8 μg. All doses were safe and well tolerated in this study; the most frequently reported adverse event was dry mouth (0–14.3% across doses; 9.5% for Placebo MDI, and 9.1% for TIO). Conclusions This study demonstrated superior bronchodilatory efficacy of GP MDI compared with Placebo MDI at all doses tested, and no serious adverse

  7. Demonstrating and assessing metered-dose inhaler-spacer technique: pediatric care providers' self-reported practices and perceived barriers.

    PubMed

    Reznik, Marina; Jaramillo, Yudilyn; Wylie-Rosett, Judith

    2014-03-01

    The National Asthma Education and Prevention Program recommends that providers demonstrate and assess metered-dose inhaler-spacer (MDI-S) technique at each medical visit. To examine practice behaviors and perceived barriers to demonstrating and assessing MDI-S technique, we surveyed pediatric providers (n = 114) at an inner-city academic medical center. While 82% of providers demonstrated MDI-S technique, only 5% of providers demonstrate the technique at every visit. Although 67% of providers assessed MDI-S technique, only 13% assess the technique at every visit. None of the providers used MDI-S checklist for assessment. Attendings were more likely than residents to demonstrate with illustrations (24% vs 6%, P = .01) and when patient's asthma was not well controlled (68% vs 47%, P = .05). Provider-identified barriers included limited access to MDI-S device, lack of time, and inadequate knowledge. Suggestions to address barriers include in-service training, device access, and nurse/health educators to alleviate the time constraints. Clinic modifications and education are needed.

  8. Dose counter performance of mometasone furoate/formoterol inhalers in subjects with asthma or COPD.

    PubMed

    Weinstein, Cindy; Staudinger, Heribert; Scott, Ian; Amar, Niran J; LaForce, Craig

    2011-07-01

    Consistent delivery of medication to treat asthma and chronic obstructive pulmonary disease (COPD) is critical for disease control. Dose tracking may eliminate the possibility of sub-therapeutic dosing. This study evaluated the overall performance, including accuracy and ruggedness, of the mometasone furoate/formoterol (MF/F) metered-dose inhaler (MDI) with an integrated numerical dose-counting mechanism in adolescent and adult subjects (aged ≥ 12 y) with persistent asthma or COPD. In a phase III, open-label, single-arm, multicenter study, subjects demonstrating at least 90% compliance with MF/F during the screening period received twice daily MF/F MDI 100/10 μg with the integrated dose counter for 4 weeks. Accuracy and ruggedness of the dose counter were assessed by the overall discrepancy rate of subject-recorded actuations versus subject-recorded dose counter readings. Discrepancy rates for Counterstrip™, a manual counting method, were evaluated for reference. Compliance and ergonomic safety were also assessed. The 233 subjects who used ≥ 90% of labeled actuations were included in the primary analysis. Of 26,317 total actuations, 33 dose counter discrepancies occurred (rate = 0.13/100 actuations), of which 13 were due to undercounting. In comparison, the Counterstrip discrepancy rate was 10-fold higher (1.34/100 actuations). Compliance with medication use, Counterstrip use, and e-diary recordings were all high (>98%). No new repetitive strain injuries or exacerbations of preexisting ergonomic injuries of the finger, hand, or arm were reported. The MF/F MDI dose counter was accurate and rugged in subjects with asthma or COPD. No new repetitive strain injuries or exacerbations of existing ergonomic injuries were associated with inhaler use. ClinicalTrials.gov identifier = NCT00604500. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. A multicenter, randomized, double-blind dose-ranging study of glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler compared to the monocomponents and open-label tiotropium dry powder inhaler in patients with moderate-to-severe COPD.

    PubMed

    Tashkin, Donald P; Martinez, Fernando J; Rodriguez-Roisin, Roberto; Fogarty, Charles; Gotfried, Mark; Denenberg, Michael; Gottschlich, Gregory; Donohue, James F; Orevillo, Chad; Darken, Patrick; St Rose, Earl; Strom, Shannon; Fischer, Tracy; Golden, Michael; Reisner, Colin

    2016-11-01

    This study formed part of the dose selection for a glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination formulated using novel Co-Suspension™ Delivery Technology and delivered via a metered dose inhaler (GFF MDI). The study aimed to confirm the optimal dose of GP to formulate with FF 9.6 μg in the fixed-dose combination product, GFF MDI. This multicenter, randomized, double-blind, chronic-dosing, balanced incomplete block, crossover study (NCT01587079) compared five doses of GFF MDI (18/9.6, 9/9.6, 4.6/9.6, 2.4/9.6 and 1.2/9.6 μg, twice daily [BID]) with its monocomponents FF MDI 9.6 μg and GP MDI 18 μg (both BID) and open-label tiotropium (18 μg once daily) as the active control. The primary efficacy endpoint was change from baseline in forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC0-12) on Day 7. In total, 159 patients were randomized to treatment and 132 patients (52.2% male, mean age 62.8 years) were included in the intent-to-treat population. All doses of GFF MDI (except 1.2/9.6 μg) resulted in statistically significant improvements in FEV1 AUC0-12 versus monocomponents and open-label tiotropium. GFF MDI 18/9.6 μg consistently showing the greatest improvement over monocomponents and open-label tiotropium. Adverse events for each GFF MDI dose were similar versus GP MDI 18 μg, FF MDI 9.6 μg and open-label tiotropium. These findings further support selection of GP 18 μg as the optimal dose to combine with FF MDI 9.6 μg for advancement into Phase III clinical trials of GFF MDI. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Combination Nicotine Metered Dose Inhaler and Nicotine Patch for Smoking Cessation: A Randomized Controlled Trial.

    PubMed

    Caldwell, Brent O; Crane, Julian

    2016-10-01

    In order to replicate the rewarding effects of smoking, nicotine replacement therapies must deliver nicotine via the pulmonary route. We aimed to measure the efficacy of a simple pressurized metered dose inhaler containing nicotine combined with a nicotine patch for smoking cessation. Double-blind randomized placebo-controlled, parallel group trial conducted at the University of Otago, Wellington, New Zealand. Five-hundred two adults (≥18 years) who smoked at least nine cigarettes per day, with a Fagerström Test for Nicotine Dependence ≥3 who wanted to quit, were randomized (1:1). active nicotine pressurized metered dose inhaler (pMDI) plus active nicotine patch, versus placebo pMDI plus active nicotine patch. Subjects were instructed to use the aerosols for 6 months when they felt an urge to smoke and the patches daily for 5 months, reduce their smoking and quit by the end of the fourth week. Subjects were followed for 7 months. The primary outcome was prolonged 6 month not smoked on 7 consecutive days, analyzed by intention-to-treat. For the primary outcome, 78/246 (31.71%) in the active group versus 46/256 (17.97%) in the control group were abstinent (odds ratio 2.12, 95% confidence interval 1.40 to 3.23). Adverse events were reported by 245/246 (99.6%) and 247/256 (96.5%) subjects in the active and control groups, respectively. Mild coughing which decreased with regular use was common with the nicotine aerosols. Inhaled nicotine from a metered dose inhaler combined with a nicotine patch substantially improves abstinence for 6 months amongst adult nicotine dependant smokers wanting to quit. In 2012, we published a systematic review of the use nicotine by inhalation in this journal. At that time we were unable to find any studies that had measured the effects of nicotine delivery by pMDI on smoking cessation, and we are not aware of any since 2012. Our study is the first to look at nicotine by pMDI in smoking cessation. The present trial demonstrates that a

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

    PubMed

    Petro, W; Schuppenies, A

    2005-05-01

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

  12. Comparative evaluation of metered-dose inhaler technique demonstration among community pharmacists in Al Qassim and Al-Ahsa region, Saudi-Arabia.

    PubMed

    Adnan, Muhammad; Karim, Shahid; Khan, Shamshir; Al-Wabel, Naser A

    2015-04-01

    Comparative evaluation of metered-dose inhaler technique demonstration among community pharmacists in Al Qassim and Al Ahsa regions, Saudi Arabia. Patients rely on the information about use of proper inhaler technique when dispensed by community pharmacists however; several studies have shown that patients are unable to show correct inhalation technique. The aim of this study is to assess the ability of community pharmacists in Al Qassim region to demonstrate proper inhalation technique of metered dose inhaler and compare the baseline outcomes with a similar study at Al-Ahsa region. We approach 96 pharmacies in Al Qassim region as mock patient (Investigator). The investigator asks the Pharmacist to guide him about proper inhalation technique of metered dose inhaler. Investigator completes a standardized and validated checklist of 8 steps of inhaler device use immediately after leaving the pharmacy. Baseline data were compared between the two study groups et al. Ahsa and Al-Qassim for variables for effectiveness of pharmacist handling of patient queries. A total number of 96 community pharmacies were approached in five cities of the Al Qassim province in Saudi Arabia This study has found that majority (93.7%) of community pharmacists failed to demonstrate proper inhalation technique of pMDI inhaler. The pharmacists demonstrated particularly poor skills involving steps for coordination of the actuation process with the mechanics of inhalation with MDI. The errors detected in this simple assessment session, if translated to patient self-medication errors, are potentially significant.

  13. Aerosol therapy by pressured metered-dose inhaler-spacer in sleeping young children: to do or not to do?

    PubMed

    Esposito-Festen, José; Ijsselstijn, Hanneke; Hop, Wim; van Vliet, Frans; de Jongste, Johan; Tiddens, Harm

    2006-08-01

    One third of young children are distressed during inhalation therapy. It has been suggested that administration during sleep could be a good alternative for these children. A laboratory study in our department using an infant upper airway model showed significantly higher lung doses from a pressured metered-dose inhaler (pMDI)-spacer for sleep-breathing patterns compared with wake-breathing patterns. We set up a daily life study to investigate the feasibility of aerosol administration by means of pMDI-spacer in sleeping young children. Over a period of 3 weeks, 30 children (age range, 6 to 23 months) with recurrent wheeze daily inhaled 1 puff of budesonide aerosol (200 mug) while awake and 1 puff during sleep. Filters positioned between the chamber and the facemask trapped the budesonide aerosol. Parents scored the child's asthma symptoms, degree of cooperation, and feasibility of administration on diary cards. In 69% of the sleep administrations, the children woke up, and in 75% of these cases the children were distressed. The mean filter dose (expressed as the percentage of the nominal dose) while awake was 47%, and during sleep it was 16% (p = 0.007). The median within-subject dose variability while awake was 50%, and during sleep it was 110% (p = 0.007). Aerosol administration by means of pMDI-spacer during sleep offers no advantage and is not a feasible treatment option in most young children.

  14. Evaluation of inhaler technique, adherence to therapy and their effect on disease control among children with asthma using metered dose or dry powder inhalers.

    PubMed

    Capanoglu, Murat; Dibek Misirlioglu, Emine; Toyran, Muge; Civelek, Ersoy; Kocabas, Can Naci

    2015-10-01

    To address the problems about correct use of inhaler devices, adherence to inhaler corticosteroid treatment and the effects of these problems on the control of asthma. Children with asthma were evaluated for the correct use of inhaler devices and adherence to therapy using a questionnaire. Effect of these on control of asthma was defined. A hundred and seventy-one patients and/or their families were interviewed. The mean age was 8.29 ± 4.65 years (1-19) and 62.6% were male. Metered dose inhaler (MDI) with spacer was used by 119 (69.5%) patients and 52 (30.5%) used dry powder inhalers (DPIs). The devices were used correctly by 68.1% of patients using MDI and 34.6% of patients using DPI (p < 0.001). The most common improper step was "breathe in from the spacer 5-6 times or 10 s" for MDI (24.4%) and "exhale to residual volume" for DPI (51.9%). Frequency of correct use was higher in patients trained 3 times (p < 0.001). Asthma was controlled more frequently among correct users (p < 0.001). Partial or poor adherence was showed 22.8% of patients. Patients with mothers who had lower educational status had higher frequency of incorrect use of inhaler device (p = 0.007). It was found that asthma control was better among correct users. Repetitive training about using devices may contribute improving inhaler technique. Especially children whose mothers had low education level and patients using DPI should be evaluated more carefully.

  15. Use of a Shared Canister Protocol for the Delivery of Metered-Dose Inhalers in Mechanically Ventilated Subjects.

    PubMed

    Gowan, Mollie; Bushwitz, Jennifer; Watts, Peggy; Silver, Patty C; Jackson, Mark; Hampton, Nicholas; Kollef, Marin H

    2016-10-01

    Mechanically ventilated patients often need bronchodilators administered via a metered-dose inhaler (MDI). Unfortunately, there are no data examining the impact of shared canister delivery of MDI therapy in mechanically ventilated patients. A prospective trial was conducted with subjects assigned to shared canister MDI therapy or single-patient canister MDI therapy. Outcomes assessed were occurrence of ventilator-associated pneumonia (VAP), hospital mortality, length of stay, ventilator-associated events, and MDI costs. Among 486 screened patients, 353 were included for analysis of which 201 (56.9%) received shared canister MDI therapy and 152 (43.1%) received single-patient canister therapy. VAP (7.0% vs 4.6%, P = .35), hospital mortality (21.9% vs 20.4%, P = .73), and ventilator days (median [interquartile range] 3.1 [0.9-7.5] d vs 2.7 [1.2-7.1] d, P = .62) were similar between the shared canister and single-patient canister groups. We did not observe clinically important differences for ventilator-associated events between study groups in our logistic regression analysis (P = .07). There was a savings of $217/subject in the shared canister group due to the use of 299 fewer MDIs. Our study found that shared canister MDI therapy compared with single-patient MDI use was associated with a significant cost savings and similar rates of VAP, hospital mortality, and length of stay but a greater prevalence of ventilator-associated events. This finding suggests that shared canister delivery of MDIs may be a cost-effective practice in mechanically ventilated patients. Based on our findings, further studies examining the overall safety of shared canister use in mechanically ventilated patients seem warranted before recommending their routine use. (ClinicalTrials.gov registration NCT01935388.). Copyright © 2016 by Daedalus Enterprises.

  16. Under pressure: predicting pressurized metered dose inhaler interactions using the atomic force microscope.

    PubMed

    Young, Paul M; Price, Robert; Lewis, David; Edge, Stephen; Traini, Daniela

    2003-06-01

    Drug particulate interactions in pressurized metered dose inhalers (pMDI) may lead to a decrease in aerosolization efficiency and subsequent efficacy in patient treatment. The interactions between salbutamol sulfate (commonly used in Ventolin pMDIs) and a series of pMDI canister materials were investigated using the atomic force microscope (AFM) colloid probe technique. Approximately 4000 individual force-distance curves were determined for a drug probe and three surfaces (10 x 10 mum areas) in situ, in a model propellant. The area under each force-distance curve was integrated to obtain separation energy values. Median separation energy values followed the rank order borosilicate glass > aluminum > PTFE, suggesting PTFE to be the most suitable canister coating.

  17. The influence of formulation variables on the performance of alternative propellant-driven metered dose inhalers.

    PubMed

    Smyth, Hugh D C

    2003-07-18

    There are a multitude of formulation factors to consider when developing a pMDI. Evaluation of each of these variables has been performed over the years, but there has been an abundance of different approaches in the determination of the effects on device performance. Thus, although much is known about pMDI on the empirical level, a systematic approach has clearly been missing. With the ratification of the Montreal Protocol and the introduction of alternative propellant systems, the opportunity to establish relationships between different levels of testing, such as in vitro measurements and in vivo outcomes, and in vivo assessments and clinical outcomes, has arrived. This review outlines research efforts that have focused on the formulation of propellant-driven metered dose inhalers using alternative propellants. These formulation factors, including device characteristics, are reviewed with respect to the performance of MDIs.

  18. Propellant-driven metered-dose inhalers for pulmonary drug delivery.

    PubMed

    Smyth, Hugh D C

    2005-01-01

    The current market for pulmonary drug delivery is at a bottleneck. The therapeutic advantages of inhalation aerosols, and the potential for the lungs as a route for systemically acting drugs, vaccines and gene therapeutic agents, have resulted in a rapid growth of the industry. Alongside this, the environment of inhaler design and formulation has changed markedly in recent years. Environmental concerns over propellants, the commercial success of dry powder inhalers, and the apparent lack of advancement of propellant-driven metered-dose inhalers (pMDIs) has led to a less clear future for these devices. This review critically assesses these pressures and also potential opportunities for the pMDI. It is proposed that the future role of pMDIs will be determined by several important forces that can be classified under 'technology development' or 'market climate' categories. Technology development forces will be strengthened by the ability of the industry to have a systematic understanding of mechanisms of spray formation, perform subsequent and continued device and formulation advances, and a focus on all patient groups: particularly paediatric and geriatric populations. The ability to succeed in these areas will be largely determined by the willingness to invest in fundamental research of pMDI technologies.

  19. 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.

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

    PubMed Central

    MacGregor, TR; ZuWallack, R; Rubano, V; Castles, MA; Dewberry, H; Ghafouri, M

    2016-01-01

    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 (Cmax), and minimum observed plasma concentration (Cmin) 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. Comparison of the systemic bioavailability of mometasone furoate after oral inhalation from a mometasone furoate/formoterol fumarate metered-dose inhaler versus a mometasone furoate dry-powder inhaler in patients with chronic obstructive pulmonary disease.

    PubMed

    Kosoglou, Teddy; Hubbell, James; Xuan, Fengjuan; Cutler, David L; Meehan, Alan G; Kantesaria, Bhavna; Wittmer, Bret A

    2013-01-01

    Coadministration of mometasone furoate (MF) and formoterol fumarate (F) produces additive effects for improving symptoms and lung function and reduces exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). The present study assessed the relative systemic exposure to MF and characterized the pharmacokinetics of MF and formoterol in patients with COPD. This was a single-center, randomized, open-label, multiple-dose, three-period, three-treatment crossover study. The following three treatments were self-administered by patients (n = 14) with moderate-to-severe COPD: MF 400 μg/F 10 μg via a metered-dose inhaler (MF/F MDI; DULERA(®)/ZENHALE(®)) without a spacer device, MF/F MDI with a spacer, or MF 400 μg via a dry-powder inhaler (DPI; ASMANEX(®) TWISTHALER(®)) twice daily for 5 days. Plasma samples for MF and formoterol assay were obtained predose and at prespecified time points after the last (morning) dose on day 5 of each period of the crossover. The geometric mean ratio (GMR) as a percent and the corresponding 90% confidence intervals (CI) were calculated for treatment comparisons. Systemic MF exposure was lower (GMR 77%; 90% CI 58, 102) following administration by MF/F MDI compared to MF DPI. Additionally, least squares geometric mean systemic exposures of MF and formoterol were lower (GMR 72%; 90% CI 61, 84) and (GMR 62%; 90% CI 52, 74), respectively, following administration by MF/F MDI in conjunction with a spacer compared to MF/F MDI without a spacer. MF/F MDI had a similar adverse experience profile as that seen with MF DPI. All adverse experiences were either mild or moderate in severity; no serious adverse experience was reported. Systemic MF exposures were lower following administration by MF/F MDI compared with MF DPI. Additionally, systemic MF and formoterol exposures were lower following administration by MF/F MDI with a spacer versus without a spacer. The magnitude of these differences with respect to systemic

  2. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Improving Metered Dose Inhaler Technique in the Emergency Department: A Prospective Study

    PubMed Central

    Richards, John R.; Luskin, Michael J.; Krivoshto, Irina N.; Derlet, Robert W.

    2004-01-01

    Objective: To determine if improvement in patients’ metered dose inhaler (MDI) technique could be achieved in the emergency department (ED) with the use of a simple illustrated instruction sheet. Methods: Prospective evaluation of a convenience sample of patients with asthma or COPD. Patients were first subjectively and objectively evaluated on their usual MDI technique, then were given an illustrated instruction sheet to study for 5 minutes. There was no verbal coaching prior to the post-test. A post-test evaluation was then performed. Results were compared using paired Student t test. Results: A total of 115 patients were enrolled. Mean age was 34.9±13.1 years, and mean years using MDI was 5.7±3.8. Subjective improvement in technique was reported by 110 patients (96%) with a mean pre-test score of 7.4±1.5 and post-test score of 9.2±1.1 (p<0.0001, 10 point scale). Objective improvement was achieved in 113 patients (98%) with a mean pre-test score of 3.9±1.3 and post-test score of 5.8±1.0 (p<0.0001, 7 point scale), corresponding to a 30% improvement in technique (95% CI: 22,39). Forty-four patients (38%) reported never having been shown proper MDI technique by a health care professional, and 112 patients (97%) found the instruction sheet helpful. Conclusions: Rapid objective and subjective improvement of MDI technique from both patients’ and physicians’ perspective is possible in the ED with the use of an illustrated instruction sheet, and requires minimal effort from the treating emergency physician. PMID:20847849

  4. Regulatory aspects of modifications to innovator bronchodilator metered dose inhalers and development of generic substitutes.

    PubMed

    Adams, W P; Poochikian, G; Taylor, A S; Patel, R M; Burke, G P; Williams, R L

    1994-01-01

    Regulatory requirements for modifications to an approved innovator metered dose inhaler (pressurized MDI; USP nomenclature: inhalation aerosol) and for development of a new generic product are discussed. Although many of the requirements apply generally to MDI's, they are discussed with specific reference to albuterol. Changes to the container and closure system may impact on the dosimetry of the redesigned product, as well as upon toxicologic and chemistry, manufacturing and controls (CMC) concerns. Changes to the formulation, including the use of alternate propellants, may raise issues requiring both clinical and in vivo performance evaluation. In view of the level of interest of a number of firms in approval requirements for generic Albuterol Inhalation Aerosol products, the article discusses in considerable detail the CMC and bioequivalence requirements for a generic product. Similarities in the CMC requirements for innovator and generic products are evident. Three comparative in vivo bioequivalence tests, particle size distribution, spray pattern and plume geometry, and unit spray content, established by the Division of Bioequivalence are discussed. Similarities and differences in the in vivo requirements for innovator and generic products are evident. Differences are the result of U.S. statute, which requires safety and efficacy testing for a product approved under a new drug application (NDA), but documentation of bioequivalence for a product approved under an abbreviated new drug application (ANDA). The advantages and disadvantages of three pharmacodynamic study designs which have potential usefulness for documentation of in vivo bioequivalence are discussed.

  5. Efficacy and cost comparisons of bronchodilatator administration between metered dose inhalers with disposable spacers and nebulizers for acute asthma treatment.

    PubMed

    Dhuper, Sunil; Chandra, Alpana; Ahmed, Aziz; Bista, Sabin; Moghekar, Ajit; Verma, Rajesh; Chong, Cynthia; Shim, Chang; Cohen, Hillel; Choksi, Sonia

    2011-03-01

    Despite demonstration of equivalent efficacy of beta agonist delivery using a metered dose inhaler (MDI) with spacer vs. nebulizer in asthma patients, use of a nebulizer remains standard practice. We hypothesize that beta agonist delivery with a MDI/disposable spacer combination is an effective and low-cost alternative to nebulizer delivery for acute asthma in an inner-city population. This study was a prospective, randomized, double-blinded, placebo-controlled trial with 60 acute asthma adult patients in two inner-city emergency departments. Subjects (n = 60) received albuterol with either a MDI/spacer combination or nebulizer. The spacer group (n = 29) received albuterol by MDI/spacer followed by placebo nebulization. The nebulizer group (n = 29) received placebo by MDI/spacer followed by albuterol nebulization. Peak flows, symptom scores, and need for rescue bronchodilatator were monitored. Median values were compared with the Kolmogorov-Smirnov test. Patients in the two randomized groups had similar baseline characteristics. The severity of asthma exacerbation, median peak flows, and symptom scores were not significantly different between the two groups. The median (interquartile range) improvement in peak flow was 120 (75-180) L/min vs. 120 (80-155) L/min in the spacer and nebulizer groups, respectively (p = 0.56). The median improvement in the symptom score was 7 (5-9) vs. 7 (4-9) in the spacer and nebulizer groups, respectively (p = 0.78). The median cost of treatment per patient was $10.11 ($10.03-$10.28) vs. $18.26 ($9.88-$22.45) in the spacer and nebulizer groups, respectively (p < 0.001). There is no evidence of superiority of nebulizer to MDI/spacer beta agonist delivery for emergency management of acute asthma in the inner-city adult population. MDI/spacer may be a more economical alternative to nebulizer delivery. Copyright © 2011. Published by Elsevier Inc.

  6. Floating patterns of metered dose inhalers.

    PubMed

    Wolf, B L; Cochran, K R

    1997-01-01

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

  7. Comparison of patient preference and ease of teaching inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers.

    PubMed

    Welch, Michael J; Nelson, Harold S; Shapiro, Gail; Bensch, George W; Sokol, William N; Smith, Joseph A; Parasuraman, Bhash M

    2004-01-01

    A multicenter, randomized, open-label, crossover study with two 4-week evaluation periods compared patient preference and ease of teaching correct inhaler technique for Pulmicort Turbuhaler versus pressurized metered-dose inhalers (pMDIs). Patients 18 to 65 years of age with stable, mild to moderate asthma, who required or were eligible for inhaled corticosteroid therapy, were randomized to treatment sequences consisting of 4-week evaluation periods with Pulmicort Turbuhaler (budesonide inhalation powder) two puffs (400 microg) bid and one of three inhaled corticosteroids via pMDI: Aerobid-M (flunisolide) four puffs (1 mg) bid, Flovent (fluticasone propionate) two puffs (440 microg) bid, or Vanceril Double Strength (beclomethasone dipropionate) five puffs (420 microg) bid. Patients indicated device preference at study end and completed the Patient Device Experience Assessment (PDEA) questionnaire after each evaluation period. Ease of teaching, time required to master use of the device, percentage of patients demonstrating mastery on the first attempt, and the number of attempts required to demonstrate mastery were assessed. Despite previous use of pMDIs by most patients, Pulmicort Turbuhaler was significantly preferred (p < 0.001) and required significantly less time to master than pMDIs (p < 0.001). Median times to device mastery were 3.67 min for Pulmicort Turbuhaler versus 5.33 min for pMDIs. Patients rated Pulmicort Turbuhaler significantly better than pMDIs on PDEA ease of use (p = 0.0005) and overall satisfaction (p < 0.0001) single-item scales and all four multi-item scales (pharyngeal symptoms, oral sensation, operational use, and inhaler attributes; p < 0.05). Overall, patients preferred Pulmicort Turbuhaler over pMDIs and required less time to be taught how to correctly use Turbuhaler trade mark.

  8. Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system.

    PubMed

    Ross, D L; Gabrio, B J

    1999-01-01

    The impending phaseout of chlorofluorocarbon (CFC)-containing metered dose inhalers (MDIs) has challenged the pharmaceutical industry to rethink and redesign many components of the technology involved in delivering asthma medication to the lungs. Along with the emergence of the first formulation using the nonozone-depleting propellant, hydrofluoroalkane (HFA) 134a to replace CFC propellants, advances in drug delivery technology have improved the performance characteristics of the MDI itself. Although MDIs have remained the mainstay of asthma therapy for 40 years, MDI technology still presents challenges. Some of the shortcomings of existing CFC MDIs affect the reliability of dosing. These challenges have been addressed in the development of the first CFC-free beta-agonist for the treatment of asthma. Airomir CFC-free (salbutamol sulfate; 3M Pharmaceuticals, St. Paul, MN), which is currently available in over 30 countries and was recently approved in the United States (Proventil HFA; Schering-Plough, Madison, NJ), incorporates numerous design and technological improvements which together with the introduction of CFC-free propellants mark the beginning of the next generation of asthma therapy. Although the new generation of CFC-free MDIs incorporates several improvements in dose reproducibility, these changes should be virtually transparent to the patient switching from a CFC MDI to a CFC-free MDI. What may be noticeable is a "softer puff," which is the result of valve and actuator redesign. The taste of the new CFC-free product may also be a little different yet totally acceptable to users.

  9. Respirable dose delivery of fluticasone propionate from a small valved holding chamber, a compact breath actuated integrated vortex device and a metered dose inhaler

    PubMed Central

    Nair, Arun; Menzies, Daniel; Barnes, Martyn; Burns, Patricia; McFarlane, Lesley; Lipworth, Brian J

    2008-01-01

    AIMS To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro-Breathe (SB) device, and pMDI Evohaler (EH). METHODS Seventeen mild to moderate asthmatics completed the study using a randomized, double-blind, double-dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose. RESULTS Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively). CONCLUSIONS The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA-FP. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Respirable dose delivery of inhaled steroids may be improved by the use of conventional valved holding chambers (such as the Aerochamber Plus spacer), but these are bulky and cumbersome to use.A novel compact breath actuated device with integrated vortex chamber (Synchro-Breathe) has been developed to overcome these problems,The lung bioavailability of inhaled fluticasone propionate is dependant on respirable dose delivery, and hence the performance of inhaler devices can be quantified by measuring the degree of adrenal suppression as a surrogate for relative lung dose. WHAT THIS STUDY ADDS This study compares the respirable dose delivery (as

  10. Recent advances in the management of obstructive airways disease. Auxiliary MDI aerosol delivery systems.

    PubMed

    Sackner, M A; Kim, C S

    1985-08-01

    Aerosol delivered through metered-dose inhalers (MDI) offers a potentially convenient way to deliver bronchodilator agents and corticosteroids to the lungs of patients with asthma and COPD. Unfortunately, most patients are unable to coordinate satisfactorily their actuation with inhalation, a problem overcome by using auxiliary MDI aerosol delivery systems. Left to their own judgment, patients often inhale the aerosol with a high inspiratory flow rather than slowly to produce optimal aerosol deposition within the airways. This problem has been corrected by one of the auxiliary MDI aerosol delivery systems (InspirEase) through auditory, visual, and tactile feedback mechanisms. MDI devices release aerosol at a high jet velocity in large particle sizes, depositing most of the aerosol in the oropharynx which can lead to potential systemic absorption of adrenergic agonists with CNS and cardiovascular side effects, oral thrush, and suppression of adrenocortical activity. All the auxiliary MDI aerosol systems promote delivery of small aerosol particles and markedly diminish oropharyngeal impaction. Of all the systems, only InspirEase provides volume and flow feedback controls to ensure an optimal inhalation maneuver. Auxiliary MDI aerosol systems should always be used for aerosolized corticosteroid administration because they minimize oropharyngeal deposition and improve aerosol delivery efficiency.

  11. Long-term safety and efficacy of glycopyrrolate/formoterol metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with chronic obstructive pulmonary disease.

    PubMed

    Hanania, Nicola A; Tashkin, Donald P; Kerwin, Edward M; Donohue, James F; Denenberg, Michael; O'Donnell, Denis E; Quinn, Dean; Siddiqui, Shahid; Orevillo, Chad; Maes, Andrea; Reisner, Colin

    2017-05-01

    The long-term safety and efficacy of a novel Co-Suspension™ Delivery Technology glycopyrrolate (GP)/formoterol fumarate (FF) 18/9.6 μg fixed-dose combination metered dose inhaler (GFF MDI) were investigated in a 28-week safety extension study (PINNACLE-3, NCT01970878) of two randomized controlled Phase III trials (PINNACLE-1 and -2; NCT01854645 and NCT01854658) in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD). Subjects completing 24 weeks' treatment with GFF MDI, GP MDI, FF MDI (all twice-daily) or open-label tiotropium 18 μg (once-daily) in PINNACLE-1 or -2 were randomly selected to continue treatment for 28 weeks. The target enrollment for PINNACLE-3 was 850 subjects. Safety and efficacy were evaluated over 52 weeks. Of 3274 subjects randomized to active treatment in PINNACLE-1 or -2, 892 entered PINNACLE-3. Incidences of adverse events, serious adverse events and major adverse cardiovascular events were similar across treatment groups with no unexpected safety findings. For change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1), treatment differences for GFF MDI versus GP MDI, FF MDI and open-label tiotropium over 52 weeks were 57, 65 and 25 mL, respectively (p ≤ 0.0117). Average daily rescue medication use was significantly reduced for GFF MDI versus GP MDI and open-label tiotropium (p ≤ 0.0002). Statistically significant improvements were observed with GFF MDI versus monocomponents in Self-Administered Computerized Transition Dyspnea Index focal score, and in St George's Respiratory Questionnaire total score versus GP MDI. Results confirmed the long-term safety and tolerability of GFF MDI 18/9.6 μg twice-daily in subjects with moderate-to-very severe COPD. Improvements in efficacy endpoints were also sustained over 52 weeks. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Recent patents in pressurised metered dose inhalers.

    PubMed

    Ehtezazi, Touraj

    2012-04-01

    In this paper recent patents in pressurised metered dose inhalers have been reviewed. The patents are related to novel valves, dose-counters, formulations, add-on devices, reduction of propellant leakage and inkjet technology. Recently patented dose-counters provide mechanisms that are less susceptible to inaccuracy, and are battery-less electronic dose-counters with the help of miniature electromechanical generators. Regarding the formulation aspect, recent patents provide methods for combinational pMDIs and more stable products. Advantages of recently patented valves are being spring-free and less subject to loss of prime. Recent developments in micromachining have allowed patents that incorporate inkjet technology to develop inhalers that are similar to pMDIs, but produce uniform aerosol droplets. Coating canisters with suitable polymers has reduced need for excipients. Recently patented add-on devices reduce aerosol deposition in the spacer by creating turbulence on the walls of the chamber. Blockage of nozzles in actuators is prevented by providing tapered nozzle channels. In conclusion, these patents show better understanding of pMDIs and provide methods to achieve products with much improved reliability, aerosol performance and stability.

  13. Protection against methacholine-induced bronchospasm: salbutamol pMDI versus Clickhaler DPI.

    PubMed

    Newhouse, M T; Patel, P; Parry-Billings, M

    2003-05-01

    Passive dry-powder inhalers (DPIs) have been developed as an alternative to pressurised metered-dose inhalers (pMDIs) to improve aerosol delivery on inhalation and eliminate the need for propellants. However, new DPI formulations of generic drugs must be rigorously compared with conventional pMDI therapy. This randomised, double-blind, double-dummy, placebo-controlled, seven-way crossover study evaluated bronchoprotection from methacholine challenge in order to compare a novel salbutamol DPI (Clickhaler) with a reference salbutamol pMDI (Ventolin). Adult asthma patients with airway hyperresponsiveness to methacholine (provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC20) <4 mg x mL(-1)) were treated on separate days with 0, 100, 200 or 400 microg of salbutamol via the DPI or pMDI. Methacholine challenge was performed before and after salbutamol treatment and the PC20 ratios analysed by Finney's bioassay to test for therapeutic equivalence of the inhalers. Eighteen patients completed the study and showed significant dose-related responses to salbutamol. The relative potency of DPI:pMDI was 1.29 (90% confidence interval 1.04-1.63). There were no treatment differences in safety (cardiac frequency, blood pressure, adverse events). Methacholine-challenge methodology provides a sensitive bioassay and has demonstrated therapeutic equivalence of the salbutamol Clickhaler dry-powder inhaler with the conventional salbutamol pressurised metered-dose inhaler.

  14. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice

    PubMed Central

    Lim, S.; Jatakanon, A.; Gordon, D.; Macdonald, C.; Chung, K. F.; Barnes, P.

    2000-01-01

    BACKGROUND—Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.
METHODS—In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 µg beclomethasone dipropionate (BDP) daily and inhaled β2 agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 µg BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 µg BDP) over a six month period was examined.
RESULTS—One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.
CONCLUSION—There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

 PMID:10992535

  15. 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.

  16. 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

  17. Lung deposition of 99mTc-radiolabeled albuterol delivered through a pressurized metered dose inhaler and spacer with facemask or mouthpiece in children with asthma.

    PubMed

    Ditcham, William; Murdzoska, Jasminka; Zhang, Guicheng; Roller, Christina; von Hollen, Dirk; Nikander, Kurt; Devadason, Sunalene G

    2014-08-01

    Research on the use of a pressurized metered dose inhaler (pMDI) with spacer (pMDI/spacer) in children has indicated oral inhalation via the spacer mouthpiece is more efficient than the combination of oral and nasal inhalation that occurs when a pMDI/spacer is used with a facemask. Changes in pMDI formulations and developments in spacer and facemask designs have highlighted the need for new comparative studies of spacer use, particularly focusing on the age at which children can be taught to transition from use of a pMDI/spacer with facemask to use of the spacer mouthpiece. Twelve children aged 3-5 years (7 males) with stable asthma were recruited. Of these, 10 children (6 males) completed both arms of the study. A transmission scan of each compliant subject was taken using a 37 MBq (99m)Tc flood source. Actuations (2-3) of a (99m)Tc-radiolabeled albuterol pMDI were administered through an antistatic spacer (OptiChamber Diamond) via either a facemask (medium LiteTouch facemask), or the spacer mouthpiece. The subject's inhalation pattern was simultaneously recorded using a pMDI Datalogger, and narrative data relating to tolerance and compliance were documented. Anterior and posterior planar scintigraphic scans were taken immediately after aerosol administration. Mean (SD) lung deposition (% total dose) was 18.1 (9.1)% with the facemask and 22.5 (7.9)% with the spacer mouthpiece (p>0.05). Peripheral lung deposition (expressed as peripheral:central (P:C) ratio) was higher in 7 out of 10 children with the facemask compared with the spacer mouthpiece: 1.3 (0.26) vs. 1.2 (0.35); (p=0.11). Head and neck deposition was higher with use of the facemask compared with the spacer mouthpiece: 19.7 (10.6)% vs. 10.8 (5.3)% (p=0.011). Lung deposition achieved using the spacer with facemask was higher than previously reported, with a difference of only 4.4% of total dose measured compared to the deposition with mouthpiece. This may be due to a combination of factors including pMDI

  18. Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler.

    PubMed

    Pickering, H; Pitcairn, G R; Hirst, P H; Bacon, P R; Newman, S P; Affrime, M B; Marino, M

    2000-12-01

    A new inhaled suspension formulation of mometasone furoate (MF), a potent corticosteroid with minimal systemic availability, has been developed for the treatment of asthma. This formulation is delivered by metered-dose inhaler (MDI) using the nonchlorofluorocarbon propellant hydrofluoroalkane 227 (HFA-227). The primary goal of this study was to determine the respiratory tract deposition of this formulation of MF. A secondary objective was to measure plasma concentrations of MF and a putative metabolite, 6-X-OH MF, to determine the systemic exposure to corticosteroid. This was a single-dose, open-label study in which 200 microg of technetium 99m (99mTc)-radiolabeled MF was administered to patients with asthma. Gamma scintigraphy was used to quantify lung, oropharyngeal, stomach, and MDI mouthpiece deposition patterns of MF. Eleven patients, aged 21 to 47 years, with a history of asthma were enrolled in and completed the study. The mean (+/- SD) whole lung deposition of MF was 13.9%+/-5.7% of the metered (ex-valve) dose. The central lung zone received 5.3%+/-2.8% of the dose; the intermediate zone received 4.7%+/-1.9%; and peripheral lung deposition was 4.0%+/-1.5%. The mean (+/- SD) ratio of peripheral to central lung deposition was 0.8+/-0.2. Oropharyngeal deposition was 79.1%+/-8.7% of the ex-valve dose, with 6.3%+/-7.8% deposited on the MDI mouthpiece and 0.7%+/-0.5% exhaled. The majority of plasma samples taken for analysis of MF and 6-13-OH MF concentrations were below the limit of quantification (50 pg/mL) in all patients after inhalation of 200 microg 99mTc-labeled ME CONCLUSION: The lung deposition of MF when administered via HFA-227 MDI is comparable to the 10 to 20% lung deposition seen with other corticosteroid suspension for- mulations administered by MDI that have demonstrated effectiveness in the treatment of asthma.

  19. 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.

  20. Aerosol deposition in the human lung following administration from a microprocessor controlled pressurised metered dose inhaler.

    PubMed Central

    Farr, S. J.; Rowe, A. M.; Rubsamen, R.; Taylor, G.

    1995-01-01

    BACKGROUND--Gamma scintigraphy was employed to assess the deposition of aerosols emitted from a pressurised metered dose inhaler (MDI) contained in a microprocessor controlled device (SmartMist), a system which analyses an inspiratory flow profile and automatically actuates the MDI when predefined conditions of flow rate and cumulative inspired volume coincide. METHODS--Micronised salbutamol particles contained in a commercial MDI (Ventolin) were labelled with 99m-technetium using a method validated by the determination of (1) aerosol size characteristics of the drug and radiotracer following actuation into an eight stage cascade impactor and (2) shot potencies of these non-volatile components as a function of actuation number. Using nine healthy volunteers in a randomised factorial interaction design the effect of inspiratory flow rate (slow, 30 l/min; medium, 90 l/min; fast, 270 l/min) combined with cumulative inspired volume (early, 300 ml; late, 3000 ml) was determined on total and regional aerosol lung deposition using the technique of gamma scintigraphy. RESULTS--The SmartMist firing at the medium/early setting (medium flow and early in the cumulative inspired volume) resulted in the highest lung deposition at 18.6 (1.42)%. The slow/early setting gave the second highest deposition at 14.1 (2.06)% with the fast/late setting resulting in the lowest (7.6 (1.15)%). Peripheral lung deposition obtained for the medium/early (9.1 (0.9)%) and slow/early (7.5 (1.06)%) settings were equivalent but higher than those obtained with the other treatments. This reflected the lower total lung deposition at these other settings as no difference in regional deposition, expressed as a volume corrected central zone:peripheral zone ratio, was apparent for all modes of inhalation studied. CONCLUSIONS--The SmartMist device allowed reproducible actuation of an MDI at a preprogrammed point during inspiration. The extent of aerosol deposition in the lung is affected by a change in

  1. A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma.

    PubMed

    Newman, Kenneth B; Milne, Scott; Hamilton, Cathy; Hall, Kent

    2002-04-01

    To determine the efficacy of albuterol by metered-dose inhaler (MDI) and spacer compared to a nebulizer. A prospective, open-label study. Large urban emergency department (ED). All consecutive adult asthma patients over a 2.5-year period. ED personnel used a standardized treatment algorithm, which included albuterol administered by nebulization, for patients presenting to the ED during the first 12 months of the study. The treatment algorithm then was switched to one that utilized albuterol administered by MDI/spacer as the primary mode of delivery for the following 18 months. As part of the conversion to MDI/spacer, ED staff counseled patients on self-management and supplied patients with a peak flowmeter, an MDI/spacer, and an inhaled steroid for home use. Pulmonary function, clinical outcome, laboratory data, and financial data were assembled and analyzed from 2,342 ED visits and 1,420 patients. While there was no significant difference in hospital admission rates between patients in the MDI/spacer group and the nebulizer group (13.2% and 14.6%, respectively), there was a statistically greater improvement in peak flow rates in the MDI/spacer group (126.8 vs 111.9 L/min, respectively; p = 0.002). The MDI/spacer group also spent significantly less time in the ED (163.6 and 175 min, respectively; p = 0.007), had a lower total albuterol dose (1,125 microg and 6,700 microg, respectively; p < 0.001), and showed a greater improvement in arterial oxygen saturation (p = 0.043). Relapse rates at 14 and 21 days were significantly lower (p < 0.01 and p < 0.05, respectively) among patients treated with the MDI/spacer and were associated with asthma education and the provision of a peak flowmeter, a spacer, and an inhaled corticosteroid for patients' home use. Albuterol administered by MDI/spacer is an efficacious and cost-effective alternative to nebulization in adults with acute asthma who present at a large urban ED.

  2. Once versus twice daily budesonide metered-dose inhaler in children with mild to moderate asthma: effect on symptoms and bronchial responsiveness.

    PubMed

    Mallol, J; Aguirre, V

    2007-01-01

    Simplifying dosing regimens could improve both adherence and asthma-related morbidity. However, there is little information on the effectiveness of once-daily budesonide, administered through a metered dose inhaler (MDI) plus spacer, on asthma symptoms and pulmonary function in asthmatic children. The aim of this study was to compare the effect of once-daily versus twice-daily doses of inhaled budesonide on symptoms, lung function and bronchial hyperresponsiveness (BHR) in asthmatic children. This study was a randomized, single-blind, parallel clinical trial. Patients received budesonide from an MDI either 800 microg as a daily dose or fractionated in 400 microg twice a day for 12 weeks. Statistical analysis was performed using tests for independent and paired samples. In both groups, asthma symptoms significantly decreased. However, the improvement in asthma symptoms, decrease in BHR and treatment adherence were significantly greater in the once-daily group than in the twice-daily group (p < 0.05). No significant differences were found between the two groups in spirometric parameters, morning peak expiratory flow or plasma cortisol values. Once-daily administration of 800 microg of inhaled budesonide administered by MDI plus spacer was more effective in controlling symptoms and improving BHR than fractionating the dose to 400 microg twice daily. The differences observed in this study could have been due to the greater adherence to treatment in patients in the once-daily group.

  3. Uncertainties on lung doses from inhaled plutonium.

    PubMed

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

    2011-10-01

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

  4. Clinical comparability between the CFC and HFA budesonide pressurised metered-dose inhalers in paediatric patients with asthma: a randomised controlled trial.

    PubMed

    Escribano, A; Tutuncu, A; Löhr, I; Carlholm, M; Polanowski, T

    2006-06-01

    To evaluate the efficacy and tolerability of a novel hydrofluoroalkane (HFA) pressurised metered dose inhaler (pMDI) formulation of budesonide (Pulmicort) versus the conventional chlorofluorocarbon (CFC) pMDI formulation in paediatric patients with asthma. This was a Phase III, multicentre, 12-week, double-blind, randomised, parallel-group study involving children (6-12 years of age) with mild to moderate asthma. Patients received either budesonide HFA pMDI or budesonide CFC pMDI 200 mug twice daily, with or without a spacer (NebuChamber/Nebunette). Primary efficacy endpoint: mean percentage change in forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Secondary efficacy endpoints included changes in FEV(1) per cent of predicted normal, forced vital capacity, morning and evening peak expiratory flow rate, asthma symptoms and use of rescue medication. A total of 159 patients received treatment (HFA 77, CFC 82). For mean percentage change in FEV(1) from baseline to week 12, the difference between the treatments (CFC pMDI - HFA pMDI) was -3.1% (95% confidence interval [CI] -8.0% to 1.8%) for the full analysis set and was not affected by spacer use. The upper CI was < 10% (the predefined non-inferiority margin), so non-inferiority was demonstrated. Improvements in the secondary efficacy endpoints with both budesonide formulations were not significantly different. In both groups there were similar numbers of adverse events and no evidence of oral candidiasis at week 12. Treatment with budesonide HFA pMDI is effective and well tolerated in children with asthma and is clinically comparable to budesonide CFC pMDI.

  5. Tolerability and in vivo performance of a novel freon-free metered dose inhaler for a fixed combinational product of reproterol and disodium cromoglycate.

    PubMed

    Hermann, R; Ruus, P; Schneider, E; de Mey, C

    1998-06-01

    The present study was conducted to describe and compare the in vivo performance (systemic exposure), clinical and laboratory safety of a fixed combinational product of inhaled reproterol (CAS 54063-54-6) plus disodium cromoglycate (DSCG; CAS 15826-37-6) using a novel freon (CFC)-free metered dose inhaler (MDI), which uses 1,1,1,2,3,3,3-heptafluoropropane (HFA-227; CAS 431-89-0) as propellant and polyoxyethylene glyceryl trioleate (Tagat TO; CAS 68958-64-5) as surfactant relative to the conventional freon-driven MDI Allergospasmin in healthy male and female volunteers. Twenty-four young male and female healthy subjects were randomly allocated in gender-balanced fashion to 4 parallel treatment groups with single and repeated dosing of either reproterol + DSCG by HFA- or CFC-MDI (each time N = 8) or placebo by HFA- or CFC-MDI (each time N = 4) using matched placebo devices thus allowing a double-blind (with regard to placebo) approach. Treatments consisted of a single morning dose of 2 actuations followed 4 days later by a 1 week treatment course of 2 actuations four times daily. Subjects were investigated extensively in terms of blood pressure, pulse rate, electrocardiography, spirometry, respiratory rate, body temperature, laboratory safety (haematology, clinical chemistry, urinalysis) and clinical well-being. There were no treatment, compound or device related effects for any of the tolerability and safety end points. The treatments were well tolerated. In particular, there was no irritative cough or any sign of broncho-irritation on application. Adverse events were reported in a total of 9 subjects: 3/8, 4/8, 0/4 and 2/4 subjects treated with reproterol + DSCG by HFA-MDI, reproterol + DSCG by CFC-MDI, placebo by HFA-MDI and placebo by CFC-MDI, respectively. Of these, 6 events in 6 subjects receiving the active treatments were considered probably or definitely related to the test drug administration (i.e. adverse drug reactions): after reproterol + DSCG one subject

  6. Comparison of the extrapulmonary beta2-adrenoceptor responses and pharmacokinetics of salbutamol given by standard metered dose-inhaler and modified actuator device.

    PubMed

    Newnham, D M; McDevitt, D G; Lipworth, B J

    1993-11-01

    1. Ten healthy subjects were randomised to inhale salbutamol via a standard metered-dose inhaler (MDI), or via a modified metered-dose actuator device (MA). Previously published radiolabelled aerosol data had shown that the MA device produced a lower aerosol velocity, reduced oropharyngeal deposition, but with unchanged pulmonary deposition. 2. Dose-response curves (DRC) were constructed with the following cumulative doses of salbutamol: 200 microg, 600 microg (200 microg + 400 microg), 1400 microg (600microg + 800 microg) ad 2600 microg (1400 + 1200 microg). Dose increments were made every 30 min and measurements of extrapulmonary beta2-adrenoceptor responses were performed 20 min after each dose. In addition, plasma salbutamol concentrations were also measured immediately before and for up to 60 min after the last dose. 3. Baseline values were not significantly different between the two study days for any of the measured parameters. 4. Cmax (ng ml(-1)) for plasma salbutamol (as means and 95% CI for difference between MA and MDI) was: 2.0 (0.3-3.7), P = 0.03. Values for t(max) (min), median and range: MA 5 (5-10) vs MDI 5 (5-10); and AUC 0-60, (ng ml(-1) min, mean and 95% CI for difference between MA and MDI): 69 (-5-143), were not significantly different between the two devices. 5. There was a significant (P < 0.01) left shift in the DRC with the MA device compared with the MDI, for hypokalaemic, finger tremor, chronotropic and electrocardiographic (Twave, Q-Tc) responses to salbutamol. Values for the hypokalaemic response (mmol l(-1)) at 2600 microg were (as change from baseline, means and 95% CI for difference between MA and MDI): 0.23 (0.10-0.36). 6. Thus, the MA device produced greater systemic absorption of salbutamol, and associated extrapulmonary beta2-adrenoceptor responses compared with a standard MDI. These results, therefore, suggest that data from radiolabelled aerosol deposition studies may not predict the systemic absorption of inhaled beta2

  7. 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

  8. In vitro comparison of the effect of inhalation delay and flow rate on the emitted dose from three valved holding chambers.

    PubMed

    Slator, Lois; von Hollen, Dirk; Sandell, Dennis; Hatley, Ross H M

    2014-08-01

    Valved holding chambers (VHCs) are accessory devices for pressurized metered dose inhalers (pMDIs). Use of a VHC may help overcome coordination issues associated with drug delivery via the pMDI alone. Previous work has established that aspects of VHC use, including the time between actuation and inhalation (inhalation delay) and inhalation flow rate, can influence the amount of drug available to inhalation. This study compared the impact of inhalation delay and flow rate on the in vitro delivery of aerosol from different VHC brands. A custom-built inhalation delay test rig, which enabled automation of controlled inhalation delays (0, 5, or 10 sec), was developed. Extraction air flow was set to 5, 15, or 30 L/min. Delivery of albuterol (ProAir HFA 90 μg) to a filter (emitted dose) was assessed using three commercially available VHC brands (one conventional, two antistatic). Emitted dose under 27 different combinations of inhalation delay, flow rate, and VHC brand was determined in order to assess the effects of inhalation delay and flow rate. Pairwise comparisons of the different VHC brands with different inhalation delay/flow rate combinations were conducted to assess in vitro equivalence. Emitted dose increased with flow rate and decreased with longer inhalation delays. Dependence on flow rate was similar for the two antistatic VHCs and more pronounced for the conventional VHC. The two antistatic VHCs showed equivalent results for the emitted dose of albuterol, across a range of flow rates and using different inhalation delays; the relation between the two antistatic VHCs fell within the ± 15% acceptance interval criteria for in vitro equivalence. The different inhalation delays and flow rates had similar effects on the delivery of drug via the three VHCs. The two antistatic VHCs were shown to be equivalent in vitro in terms of emitted dose of albuterol.

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

    PubMed

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

    1999-09-10

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

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

    PubMed Central

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

    1990-01-01

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

  11. Home-made spacer as an auxiliary device in administration of beclomethasone via pressurized metered dose inhaler for asthma control. A randomized controlled pragmatic trial.

    PubMed

    Schor, Deborah; Rizzo, José Ângelo; Medeiros, Decio; Dela Bianca, Ana Carolina; Silva, Almerinda Rego; Nunes, Carlos; Morais-Almeida, Mário; Sarinho, Emanuel

    2017-05-01

    Holding chambers or spacers can enhance the efficacy of pressurized metered dose inhalers (pMDI) in delivering inhaled medications, as they reduce the need for hand-breath coordination and improve lower airways deposition. Nevertheless, their cost can be high for patients in low-income countries. To compare asthma control achieved with beclomethasone-dipropionate administered through a hydrofluoroalkane-driven pMDI (BDp-pMDI) coupled to a home-made spacer (HmS) or to a valved commercial spacer (VCS) as auxiliary devices. Sixty-three patients with poorly controlled asthma that had a BDp-pMDI prescription were randomized to use the inhaler coupled to a HmS made of 500 ml plastic bottles (Group HmS, n = 32) or to a VCS (Group VCS, n = 31) for 60 days. All were given training sessions. Asthma control was assessed through the Asthma Control Test (ACT) and forced expiratory volume in the first second (FEV1), both measured before, and 30 and 60 days after treatment began. Both groups showed significant improvement in ACT scores after 30 and 60 days compared to baseline values (an increase of 7 and 7.8 points for the HmS group and 5.9 and 7.0 points for the VCS group, respectively, p < 0.001). There was no statistically significant difference in ACT scores between groups at any observation time (P = 0.261). FEV1 showed the same behavior. A similar level of asthma control was achieved with beclomethasone-dipropionate administered through a pMDI whether the inhaler was coupled to the HmS or VCS. These results are significant for asthma control planning strategies in low-income communities. (Trial Register Number: RBR-5x4dc9). Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

    Aswania, Osama; Chrystyn, Henry

    2002-05-01

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

  13. Comparison of optical particle sizing and cascade impaction for measuring the particle size of a suspension metered dose inhaler.

    PubMed

    Pu, Yu; Kline, Lukeysha C; Khawaja, Nazia; Van Liew, Melissa; Berry, Julianne

    2015-05-01

    Optical techniques for the particle size characterization of metered dose inhaler (MDI) suspensions have been developed as an alternative to the labor-intensive and time-consuming impaction method. In this study, a laser diffraction (LD) apparatus with a liquid cell ("wet cell" method) and a "time-of-flight" apparatus named aerodynamic particle sizer (APS) were utilized to assess MDI suspensions with varied formulation compositions and storage conditions. The results were compared with the conventional Anderson cascade impaction (ACI) data. The two optical methods were able to detect the changes in particle size distributions between formulations, yet to a lesser extent than those observed using the cascade impaction methodology. The median aerodynamic particle size measured by the APS method and the median geometric particle size obtained from the LD method were linearly correlated with the corresponding ACI results in the range of 2-5 µm. It was also found that the APS measurement was biased towards the finer particle size region and resulted in overestimated fine particle fraction (FPF) values which were 2-3 times folds of the ACI results. In conclusion, the optical particle sizing techniques may, under some circumstances, be viable techniques for the rapid assessment of MDI suspensions. The "wet cell" LD method, in particular, is found to be a valuable means of detecting active pharmaceutical ingredient (API) particle size changes in an MDI suspension. Using both the LD and the APS methods in early formulation screening followed by a final assessment with cascade impaction analysis can improve the efficiency of MDI formulation development.

  14. The effect of reduction of propellant mass fraction on the injection profile of metered dose inhalers.

    PubMed

    Ju, Dehao; Shrimpton, John; Hearn, Alex

    2010-05-31

    In order to provide an improved understanding of the flow in pressurized-metered dose inhalers (pMDIs), especially monitoring the output temperature and mass flow rate to obtain maximum atomization efficiency from the available energy, a numerical model for a two phases, multi-component compressible flow in a pressurized-metered dose inhaler is presented and validated. It is suitable for testing with various formulations and different geometries for a range of pMDI devices. We validated the model against available data in the literature for a single component HFA 134a propellant, and then investigated the response of the model to other formulations containing non-volatile components. Further validation is obtained by an experiment using the dual beam method which acquired the actuation flow properties such as spray velocity and duration. The deviation of the numerical predictions for the peak exit velocity against the experimental results is 5.3% and that for effective spray duration 5.0%. From the numerical and experimental results, it is found that for the formulations with the mass fraction of HFA 134a>80%, the effective spray duration of the pMDI is around 0.1s. Furthermore the droplet peak exit velocity at the axial station x=25 mm from the actuation nozzle decreases from 20 to 15m/s with the reduction of the propellant (HFA 134a) from 95%. Formulations with the mass fraction of HFA 134a below 80% produce poor quality spray which is indicated from the unsteady peak exit velocity, changeable spray number density in each experimental test, and numerical simulations also confirmed the non-viability of this condition. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  15. 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

  16. Cost-effectiveness of metered-dose inhalers for asthma exacerbations in the pediatric emergency department.

    PubMed

    Doan, Quynh; Shefrin, Allan; Johnson, David

    2011-05-01

    To compare the incremental cost and effects (averted admission) of using a metered-dose inhaler (MDI) against wet nebulization to deliver bronchodilators for the treatment of mild to moderately severe asthma in pediatric emergency departments (EDs). We measured the incremental cost-effectiveness from the perspective of the hospital, by creating a model using outcome characteristics from a Cochrane systematic review comparing the efficacy of using MDIs versus nebulizers for the delivery of albuterol to children presenting to the ED with asthma. Cost data were obtained from hospitals and regional authorities. We determined the incremental cost-effectiveness ratio and performed probabilistic sensitivity analyses using Monte Carlo simulations. Using MDIs in the ED instead of wet nebulization may result in net savings of Can$154.95 per patient. Our model revealed that using MDIs in the ED is a dominant strategy, one that is more effective and less costly than wet nebulization. Probabilistic sensitivity analyses revealed that 98% of the 10 000 iterations resulted in a negative incremental cost-effectiveness ratio. Sensitivity analyses around the costs revealed that MDI would remain a dominant strategy (90% of 10 000 iterations) even if the net cost of delivering bronchodilators by MDI was Can$70 more expensive than that of nebulized bronchodilators. Use of MDIs with spacers in place of wet nebulizers to deliver albuterol to treat children with mild-to-moderate asthma exacerbations in the ED could yield significant cost savings for hospitals and, by extension, to both the health care system and families of children with asthma.

  17. 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).

  18. In vitro reporter gene transfection via plasmid DNA delivered by metered dose inhaler.

    PubMed

    Bains, Baljinder K; Birchall, James C; Toon, Richard; Taylor, Glyn

    2010-07-01

    Aerosolised DNA administration could potentially advance the treatment of inheritable lung diseases, lung malignancies and provide genetic immunisation against infection. Jet nebulisation, the current standard for introducing DNA formulations into the lung, is inherently inefficient. Pressurised metered dose inhalers (pMDIs) offer a potentially more efficacious and convenient alternative, especially for repeat administration. We aim to modify a novel low-energy nanotechnology process to prepare surfactant-coated pDNA nanoparticles for pulmonary gene delivery via a pMDI. Water-in-oil microemulsions containing green fluorescent protein reporter plasmid were snap-frozen and lyophilised. Lyophilised pDNA, in some cases following a surfactant wash, was incorporated into pMDIs with hydrofluoroalkane 134a (HFA134a) propellant and ethanol as cosolvent. To assess biological functionality, A549 human lung epithelial cells were exposed to aerosolised pDNA particles in the presence of dioleoyl-trimethylammonium propane (DOTAP). Transfection studies demonstrated that pDNA biological functionality was maintained following aerosolisation. In vitro toxicity assays (MTT) showed no significant cell viability loss following aerosolised pDNA treatment. We have demonstrated that pDNA particles can be incorporated into an HFA134a formulation and aerosolised using a standard valve and actuator. Particles prepared by this novel process have potential for stable and efficient delivery of pDNA to the lower respiratory tract via standard pMDI technology.

  19. Determination of physical and chemical stability in pressurised metered dose inhalers: potential new techniques.

    PubMed

    Ooi, Jesslynn; Traini, Daniela; Boyd, Ben J; Gaisford, Simon; Young, Paul M

    2015-01-01

    Pressurised metered dose inhalers (pMDIs) are subject to rigorous physical and chemical stability tests during formulation. Due to the time and cost associated with product development studies, there is a need for online techniques to fast screen new formulations in terms of physical and chemical (physico-chemical) stability. The problem with achieving this is that pMDIs are by their definition, pressurised, making the direct observation of physico-chemical properties in situ difficult. This review highlights the characterisation tools that can enhance the product development process for pMDIs. Techniques investigated include: laser diffraction, Raman spectroscopy, isothermal ampoule calorimetry, titration calorimetry and gas perfusion calorimetry. The operational principles behind each technique are discussed and complemented with examples from the literature. Laser diffraction is well placed to analyse real-time physical stability as a function of particle size; however, its use is restricted to suspension pMDIs. Raman spectroscopy can be potentially used to attain both suspension and solution pMDI spectra in real time; however, the majority of experiments are ex-valve chemical composition mapping. Calorimetry is an effective technique in capturing both chemical and physical degradations of APIs in real time but requires redevelopment to withstand pressure for the purposes of pMDI screening.

  20. 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

  1. Swellable hydrogel particles for controlled release pulmonary administration using propellant-driven metered dose inhalers.

    PubMed

    Selvam, Parthiban; El-Sherbiny, Ibrahim M; Smyth, Hugh D C

    2011-02-01

    Swellable hydrogel microparticle-based pressurized metered dose inhaler (pMDI) formulations allow delivery of small respirable sized particles (1-5 microns), which swell upon the deposition in the deep lung and therefore can elude alveolar macrophage uptake via their larger geometric sizes. In addition, optimized surface chemistry may allow for sustained release of drug for multiple days. Drug-loaded PLGA nanoparticles encapsulated in PEG/chitosan (Cs) graft copolymer-based hydrogel microparticles were synthesized and characterized. Physical stability of dispersions within Hydrofluoroalkane propellant systems was assessed. The formulations were evaluated for aerosolization performance using a Next Generation Impactor. Low density PEG/chitosan (Cs) graft copolymer-based hydrogel microparticles containing drug-loaded PLGA nanoparticles has an average diameter of 1-2 μm. These dispersions showed good compatibility with HFA227ea. Suspension stability was found to vary with the concentration of hydrogel particles. It was typically between 1 to 5 min and was found to be easily redispersible. Aerosolization studies showed fine particle fraction as high as 65% could be achieved. These swellable hydrogel-based microparticle pMDI formulations could be used as potential delivery vehicles for nanoparticle therapeutics.

  2. Salbutamol with metered dose inhalers with spacers - an established emergency treatment for preschool wheeze.

    PubMed

    Mecklin, Minna; Paassilta, Marita; Korppi, Matti

    2012-11-01

    Metered dose inhalers (MDI) with spacers were implemented to treat preschool wheeze in the emergency room (ER) and hospital in 2006 in our children's hospital. The implementation at day time happened successfully within 4 months, but not at night time. The objective of the present study was to check the treatment mode, hospitalization rate and length of hospital stay (LOS) 4 years later. The present retrospective hospital chart review was identical to the review 4 years earlier, including data collection on treatment mode in 1- to-5-year-old preschool wheezers in the ER, on need of hospitalization, on treatment mode in hospital and on LOS. Both studies were performed during the same late-autumn and early-winter months. In the ER, 96% of the children with preschool wheeze were treated with salbutamol using MDIs with spacers. Hospitalization rate was 51%, and all but one were treated with MDIs with spacers in hospital at both day and night time. Mean LOS was 2.48 days, being shorter than 4 years earlier. Administration of salbutamol using MDI with spacer became an established emergency treatment of preschool wheeze within 4 years after the initial change from nebulizers to MDIs with spacers. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  3. Pressurised metered dose inhalers with spacers versus nebulisers for beta-agonist delivery in acute asthma in children in the emergency department.

    PubMed

    Boyd, R; Stuart, P

    2005-09-01

    Wet nebulisers are widely used for beta-2 agonist delivery in Australasian emergency departments (ED). An increasing body of work suggests that pressurised metered dose inhalers with spacers (pMDI-S) are as effective. This study aims to investigate the effect on admission rates, total time in the ED, and total time in hospital after initiation of routine pMDI-S treatment for mild to moderate asthma in children presenting to the ED. Children with a discharge diagnosis of asthma were identified over sequential 3 month time periods. In the first period, wet nebuliser treatment was routine and in the subsequent trial period pMDI-S treatment was instituted as routine. Admissions rates, total time in hospital, and total time in the ED were recorded for each group. Admission rates fell significantly from 31% to 20.6% after routine use of pMDI-S treatment. There was a non-significant trend to an increase in total ED and total hospital times. Introduction of routine pMDI-S treatment in the paediatric ED results in a significant drop in admission rates but no significant change in total hospital times or total ED times.

  4. Metered-dose inhalers: actuators old and new.

    PubMed

    Lewis, David

    2007-05-01

    The actuator has been the patient interface of the metered-dose inhaler for the past 50 years. The original 1956 design remains a significant influence upon today's actuators and, moreover, its distinct geometry is still recognisable on the market. The actuator has contributed to the metered-dose inhaler's success as a clinically effective and cost-effective device. This review focuses upon developments since the actuator's introduction as an integral part of the metered-dose inhaler and discusses key aspects of its design that influence lung deposition potential. The ability of the actuator to reduce unwanted oropharyngeal drug deposition, facilitate correct patient use and provide valuable patient feedback is highlighted.

  5. Optimizing the primary particle size distributions of pressurized metered dose inhalers by using inkjet spray drying for targeting desired regions of the lungs.

    PubMed

    Ehtezazi, T; Davies, M J; Seton, L; Morgan, M N; Ross, S; Martin, G D; Hutchings, I M

    2015-02-01

    Conventional suspension pressurized metered dose inhalers (pMDIs) suffer not only from delivering small amounts of a drug to the lungs, but also the inhaled dose scatters all over the lung regions. This results in much less of the desired dose being delivered to regions of the lungs. This study aimed to improve the aerosol performance of suspension pMDIs by producing primary particles with narrow size distributions. Inkjet spray drying was used to produce respirable particles of salbutamol sulfate. The Next Generation Impactor (NGI) was used to determine the aerosol particle size distribution and fine particle fraction (FPF). Furthermore, oropharyngeal models were used with the NGI to compare the aerosol performances of a pMDI with monodisperse primary particles and a conventional pMDI. Monodisperse primary particles in pMDIs showed significantly narrower aerosol particle size distributions than pMDIs containing polydisperse primary particles. Monodisperse pMDIs showed aerosol deposition on a single stage of the NGI as high as 41.75 ± 5.76%, while this was 29.37 ± 6.79% for a polydisperse pMDI. Narrow size distribution was crucial to achieve a high FPF (49.31 ± 8.16%) for primary particles greater than 2 µm. Only small polydisperse primary particles with sizes such as 0.65 ± 0.28 µm achieved a high FPF with (68.94 ± 6.22%) or without (53.95 ± 4.59%) a spacer. Oropharyngeal models also indicated a narrower aerosol particle size distribution for a pMDI containing monodisperse primary particles compared to a conventional pMDI. It is concluded that, pMDIs formulated with monodisperse primary particles show higher FPFs that may target desired regions of the lungs more effectively than polydisperse pMDIs.

  6. 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

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

    PubMed Central

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

    2014-01-01

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

  8. In Vitro Comparison of Output and Particle Size Distribution of Budesonide from Metered-Dose Inhaler with Three Spacer Devices during Pediatric Tidal Breathing.

    PubMed

    Kamin, Wolfgang; Ehlich, Hilke

    2006-01-01

    The aim of this in vitro study was to determine the delivered dose of budesonide 200mug via a chlorofluorocarbon-free pressurized metered dose inhaler (pMDI) when administered through different spacers in tidal breathing patterns of young children. Tidal breathing was simulated for toddlers and children. Spacers tested were Babyhaler((R)), AeroChamber((R)) Plus small and medium; the pMDI was Budiair((R)) 200microg. Output was measured after one actuation and five inhalations in primed and unprimed spacers. Cumulated output was evaluated after each of five simulated inhalations. Aerosol characteristics - i.e. particle size distribution of the output - were determined in primed spacers with a cascade impactor using high-performance liquid chromatography and UV detection. Total output from primed spacers after five inhalations was determined between 37.9microg and 40.9microg with little differences between spacers and breathing patterns. About 58-79% of this total output was inhaled with the first breath from the AeroChamber((R)) Plus and about 26% from the Babyhaler((R)). The fine particles <5mum ranged between 87% and 92% of the delivered dose for all three spacers. The nominal dose (200microg) of the Budiair((R)) 200microg inhaler is reduced to 40microg delivered dose or less by using Babyhaler((R)) and AeroChamber((R)) Plus spacers taking five breaths. With a single breath the delivered dose can be reduced further to a minimum of 10microg using the Babyhaler((R)). Clinical studies are warranted in the future for decisions on 'clinical efficacy', safety, and exact dose adjustment.

  9. High-Speed Laser Image Analysis of Plume Angles for Pressurised Metered Dose Inhalers: The Effect of Nozzle Geometry.

    PubMed

    Chen, Yang; Young, Paul M; Murphy, Seamus; Fletcher, David F; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

    2017-04-01

    The aim of this study is to investigate aerosol plume geometries of pressurised metered dose inhalers (pMDIs) using a high-speed laser image system with different actuator nozzle materials and designs. Actuators made from aluminium, PET and PTFE were manufactured with four different nozzle designs: cone, flat, curved cone and curved flat. Plume angles and spans generated using the designed actuator nozzles with four solution-based pMDI formulations were imaged using Oxford Lasers EnVision system and analysed using EnVision Patternate software. Reduced plume angles for all actuator materials and nozzle designs were observed with pMDI formulations containing drug with high co-solvent concentration (ethanol) due to the reduced vapour pressure. Significantly higher plume angles were observed with the PTFE flat nozzle across all formulations, which could be a result of the nozzle geometry and material's hydrophobicity. The plume geometry of pMDI aerosols can be influenced by the vapour pressure of the formulation, nozzle geometries and actuator material physiochemical properties.

  10. The effect of actuator nozzle designs on the electrostatic charge generated in pressurised metered dose inhaler aerosols.

    PubMed

    Chen, Yang; Young, Paul M; Fletcher, David F; Chan, Hak Kim; Long, Edward; Lewis, David; Church, Tanya; Traini, Daniela

    2015-04-01

    To investigate the influence of different actuator nozzle designs on aerosol electrostatic charges and aerosol performances for pressurised metered dose inhalers (pMDIs). Four actuator nozzle designs (flat, curved flat, cone and curved cone) were manufactured using insulating thermoplastics (PET and PTFE) and conducting metal (aluminium) materials. Aerosol electrostatic profiles of solution pMDI formulations containing propellant HFA 134a with different ethanol concentration and/or model drug beclomethasone dipropionate (BDP) were studied using a modified electrical low-pressure impactor (ELPI) for all actuator designs and materials. The mass of the deposited drug was analysed using high performance liquid chromatography (HPLC). Both curved nozzle designs for insulating PET and PTFE actuators significantly influenced aerosol electrostatics and aerosol performance compared with conducting aluminium actuator, where reversed charge polarity and higher throat deposition were observed with pMDI formulation containing BDP. Results are likely due to the changes in plume geometry caused by the curved edge nozzle designs and the bipolar charging nature of insulating materials. This study demonstrated that actuator nozzle designs could significantly influence the electrostatic charges profiles and aerosol drug deposition pattern of pMDI aerosols, especially when using insulating thermoplastic materials where bipolar charging is more dominant.

  11. Comparative efficacy of terbutaline sulphate delivered by Turbuhaler dry powder inhaler or pressurised metered dose inhaler with Nebuhaler spacer in children during an acute asthmatic episode.

    PubMed

    Drblik, S; Lapierre, G; Thivierge, R; Turgeon, J; Gaudreault, P; Cummins-McManus, B; Verdy, I; Haddon, J; Lee, J; Spier, S

    2003-04-01

    To compare the efficacy of terbutaline sulphate delivered via Turbuhaler with a pressurised metered dose inhaler (pMDI) connected to Nebuhaler spacer in a population of asthmatic children presenting to emergency departments because of an acute episode of asthma. Randomised double blind, double dummy, parallel study of acute asthma in the emergency department. A total of 112 children (6-16 years), who had a diagnosis of asthma, a baseline FEV1 of 25-60% of predicted normal value (PNV), and the ability to perform spirometry were studied. Patients received two doses of 0.5 mg/10 kg (maximum 2.0 mg) of terbutaline sulphate at time 0 minutes and time 30 minutes. The two groups were also stratified into subgroups based on FEV1: 25-45% and 45.1-60% PNV. FEV1 before treatment and at two 15-minute intervals after each treatment was the main outcome measure. PIF, PEF, heart rate, SpO2, and tremor were also measured at these times. Both the Turbuhaler and pMDI+Nebuhaler groups showed significant increases from baseline to final value in their FEV1 results, 49% and 50% change from baseline to t = 60 min, respectively (p < 0.001) using last value carried forward. No significant difference was found between the two groups for these results. Subanalysis of the stratified groups revealed similar results. In addition, no significant difference was found in the group and subgroup comparisons for heart rate, SpO2, and tremor. Results show that Turbuhaler and pMDI+Nebuhaler are similar in terms of benefit and side effects in the treatment of acute moderate to severe asthma attacks in this study population.

  12. Comparing MDI and DPI aerosol deposition using in vitro experiments and a new stochastic individual path (SIP) model of the conducting airways.

    PubMed

    Longest, P Worth; Tian, Geng; Walenga, Ross L; Hindle, Michael

    2012-06-01

    Deposition characteristics of MDI and DPI aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a newly developed stochastic individual path (SIP) model for different inhalation profiles. In vitro experiments were used to determine initial particle distribution profiles and to validate computational fluid dynamics (CFD) model results for a MDI and DPI delivering the same dose of drug in a geometry of the mouth-throat and tracheobronchial airways. The validated CFD model was then used to predict the transport and deposition of the drug using correct and incorrect inhalation profiles for each inhaler. The MDI delivered approximately two times more drug to the tracheobronchial region compared with the DPI for both correct and incorrect inhalation profiles. Errors in inhalation reduced the deposited tracheobronchial dose by approximately 30% for both inhalers. The DPI delivered the largest dose to the mouth-throat (~70%) and the MDI delivered the largest dose to the alveolar airways (~50%). The developed in silico model provides new insights into the lung delivery of pharmaceutical aerosols and can be applied in future studies in combination with pharmacokinetic analysis to establish bioequivalence between devices.

  13. Evaluation of Metered Dose Inhaler Use Technique and Response to Educational Training.

    PubMed

    Jolly, G P; Mohan, A; Guleria, R; Poulose, Rosemary; George, J

    2015-01-01

    Prescribing inhalers without imparting adequate education regarding proper technique of their usage may result in suboptimal clinical improvement and wastage of medication. Training interventions using a standard check-list may help improve faulty techniques and enhance drug efficacy. Patients using metered dose inhaler (MDI) were included in the study. Inhaler technique was first evaluated at baseline using a standard check-list of recommended steps (National Institute of Health guidelines; see Table) and scores were given for each step correctly performed. Those who could not perform all steps correctly were given training intervention. The patients were assigned to two methods of educational intervention; one group was trained by providing written material giving step-wise instructions while the other group was given an actual physical demonstration using a placebo device. The technique was re-evaluated and scored following each educational session, and continued till the patient achieved a full score, or for a maximum of 3 sessions, whichever occurred earlier. Median score was calculated after each session and was compared between the two groups. Each patient was followed up after two months and the re-evaluated the same way. One hundred and seventeen subjects were enrolled in the study (59 in the written group and 57 in the practical demonstration group). At baseline, only 1 of the 117 subjects could perform all the steps of inhaler usage correctly. This patient was, therefore, not provided the inhaler technique education. The overall median (range) score of the whole group was 3 (range 1-8). This score rose to 6, 7 and 8 after each of the three subsequent educational intervention sessions. At one-month follow-up, the median score dropped to 7 and improved with a repeat educational session as previously done. A significant difference was observed in the median score improvement achieved in the practical demonstration group compared with the written instruction

  14. Measurements of electrodynamic effects on the deposition of MDI and DPI aerosols in a replica cast of human oral-pharyngeal-laryngeal airways.

    PubMed

    Ali, Mohammed; Mazumder, Malay K; Martonen, Ted B

    2009-03-01

    Metered dose inhalers (MDIs) and dry powder inhalers (DPIs) are popular drug delivery devices used in the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Integrated effects of electrostatic charges and aerodynamic sizes on the deposition of MDI and DPI particles in a replica cast of human oral-pharyngeal-laryngeal (OPL) airways were examined. Experimental aerosols were generated from commercially available MDI and DPI devices. They are the trademarked brands of the same pharmaceutical company, and contain the same amounts of different drugs. Inhalations were administered as boluses and characterized with an Electronic Single Particle Aerodynamic Relaxation Time (ESPART) analyzer before and after passing through the cadaver-based OPL cast. The MDI and DPI aerosols were not only of different sizes but also carried different positive, negative and zero electrostatic charges; 42.2% of the total number of DPI particles was charged in comparison to 6% of those produced by the MDI. Electrodynamic properties (e.g., charges and sizes) played significant roles on the behavior and deposition of aerosols in the OPL airways. As detailed herein, deposition fractions of the total (charged and uncharged) DPI aerosols were 21.5% in contrast to 2.8% for the MDI aerosols, whereas the charged particle deposition for the DPI was 46.7% in contrast to 22.5% for the MDI. Particle losses in the OPL passages were greater for the DPI than the MDI as the former generated more charged particles than the latter. This finding is consistent with results reported by other researchers but contradicts the observation of another investigator where MDI losses were reported as being higher than those for DPIs. The chief reason for this difference may be that the latter study did not account for the electrical properties of aerosol particles, but only for their mechanical properties. Because the measured deposition efficiencies of MDI and DPI aerosols

  15. In vitro performance characteristics of valved holding chamber and spacer devices with a fluticasone metered-dose inhaler.

    PubMed

    Asmus, Michael J; Liang, Judy; Coowanitwong, Intira; Hochhaus, Gunther

    2004-02-01

    To compare the in vitro aerosol deposition characteristics of several commercially available valved holding chamber (VHC) and spacer devices used with a fluticasone metered-dose inhaler (MDI). In vitro aerosol deposition study University-affiliated research center. Seven VHC devices: BreatheRite, E-Z Spacer, EasiVent, AeroChamber, InspirEase, OptiChamber, and Space Chamber. Six spacer devices: OptiHaler, Aerosol Cloud Enhancer (ACE), Gentle-Haler, MediSpacer, Ellipse, and a 6-inch tube (1-inch inside diameter). The respirable dose (aerosol particles 1-5 microm) of fluticasone was determined by sampling 10 220-microg actuations from five runs with each spacer or VHC plus MDI combination, by using a well-established in vitro cascade impactor method. Fluticasone aerosol was washed from the impactor with methanol and quantified by means of high-performance liquid chromatography. Differences among outcomes were determined with analysis-of-variance testing. Among spacers, Ellipse had the highest respirable dose (104 microg, p < 0.01). Respirable doses for the 6-inch tube (74.3 microg), Gentle-Haler (81.7 microg), and MediSpacer (82.6 microg) were no different from that of the MDI (p > 0.05), whereas respirable doses of OptiHaler (44.6 microg) and ACE (47.2 microg) were less than those of all other spacers (p < 0.001). Among VHC devices, respirable doses from EasiVent (35.6 microg), AeroChamber (47.0 microg), InspirEase (52.7 microg), OptiChamber (53.1 microg), and Space Chamber (58.3 microg) were not different (p > 0.05), whereas BreatheRite (13.1 microg) and E-Z Spacer (27.3 microg) respirable doses were less than those of the other VHC devices (p < 0.05). Spacers and VHC devices available in the United States do not demonstrate equivalent in vitro performance with the fluticasone MDI. The difference between highest and lowest respirable doses in each device category would likely lead to clinically relevant differences in the quantity of fluticasone delivered to a

  16. A Cost Analysis of Salbutamol Administration by Metered-Dose Inhalers with Spacers versus Nebulization for Patients with Wheeze in the Pediatric Emergency Department: Evidence from Observational Data in Nova Scotia.

    PubMed

    Spin, Paul; Sketris, Ingrid; Hill-Taylor, Barbara; Ward, Courtney; Hurley, Katrina F

    2017-01-01

    Despite evidence demonstrating the advantages of metered-dose inhalers with spacers (MDI-s), nebulization (NEB) remains the primary method of asthma treatment in some pediatric emergency departments (PEDs). There is a perception that delivering salbutamol by MDI-s is more costly than by NEB. This research evaluates the relative costs of MDI-s and NEB using local, hospital-specific, patient-level data. Regression models estimated associations between the salbutamol inhalation method and costs, length of stay (LOS) in the PED and hospital, and the probability of admission. Our population was a random sample of 822 patients presenting with wheeze to the PED in 2008/2009. Control variables included age, sex, triage acuity, time of PED visit, other medications, and vitals. Costs were calculated using the prices and quantities of medical resources used per treatment. Probabilistic sensitivity analysis was used. Treatment with MDI-s versus NEB was associated with an absolute decrease in hospitalization of 4.4% (p<0.05) and a 25-hour (p<0.001) reduction in average inpatient stay, after controlling for triage acuity and patient characteristics. This resulted in savings of $24/patient in the PED and $180/patient overall (p<0.001). Inpatient care accounted for more than 90% of total patient costs. Our results suggest economic gains associated with MDI-s for salbutamol inhalation in PEDs. Sensitivity analyses show that this conclusion is not affected by changes in model parameters that may differ by jurisdiction. Since most facilities already collect the data used for this study, our methods could be adopted for a cross-jurisdictional account of the cost effectiveness of MDI-s.

  17. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    PubMed

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  18. Pharmacokinetics of epimeric budesonide and fluticasone propionate after repeat dose inhalation – intersubject variability in systemic absorption from the lung

    PubMed Central

    Minto, Charles; Li, Benny; Tattam, Bruce; Brown, Ken; Seale, J Paul; Donnelly, Richard

    2000-01-01

    Aims Pharmacokinetic variability is likely to be a significant factor contributing to the interindividual differences in dose requirements, anti-inflammatory response and side-effects with inhaled corticosteroids (ICS), but there is limited information about the disposition of ICS during regular dosing with a pressurized metered dose inhaler (pMDI). This study uses a mixed effects modelling approach to quantify and compare the interindividual variability in pharmacokinetics of epimeric budesonide (BUD) and fluticasone propionate (FP) after repeat-dose inhalation. Methods This pharmacokinetic substudy was part of a previously published open-label, randomised, placebo-controlled, 7-period crossover study to evaluate the short-term effects on plasma cortisol levels of inhaled BUD (400, 800, 1600 µg twice daily) and FP (375, 750, 1000 µg twice daily) via pMDI in a group of healthy male volunteers. On the fifth day of each high-dose treatment period (BUD 1600 µg twice daily and FP 1000 µg twice daily), venous blood samples were collected in nine subjects prior to the last dose and at 15 min, 30 min, 1, 2, 4, 6 and 8 h postdose for measurement of plasma drug concentrations to determine the pharmacokinetics of epimeric BUD and FP following inhalation. Non-compartmental analysis and a mixed effects model were used to characterize the disposition profiles. Results Both drugs had a rapid absorption half-life (BUD 10 min vs FP 11.3 min), but quite different elimination half-lives (BUD 2.4 h vs FP 7.8 h). Although there were intraindividual differences in the handling of the 22R-and 22S-epimers of BUD, there were no consistent pharmacokinetic differences between the two enantiomers in the group as a whole. Consistent with previous reports of FP’s higher volume of distribution (V) and lower systemic bioavailability (F), the V/F ratio was lower for BUD than FP (498 l vs 8100 l). The parameter with the greatest interindividual variability for both BUD and FP was the rate of

  19. Accuracy of inhaler use in patients with chronic obstructive pulmonary disease.

    PubMed

    Lee, Haejung; Boo, Sunjoo; Lim, Yeonjung; Kim, Sungmin; Kim, In-Ah

    2014-10-01

    Inaccurate use of medication inhalers can reduce effectiveness, patient adherence, and disease stability. Therefore, the accurate use of inhalers in patients with chronic obstructive pulmonary disease (COPD) is crucial. This cross-sectional study evaluated 196 Korean patients with COPD for step-by-step accuracy of inhaler use with four different types of inhalers (metered-dose inhaler [MDI], Turbuhaler, Diskus, and HandiHaler); differences in accuracy levels by sociodemographic or clinical characteristics were evaluated. Descriptive statistics and t tests were used for data analysis. The proportion of patients with completely accurate inhaler use was low, ranging from 21.9% (Turbuhaler) to 46.2% (MDI). Errors with all types of inhalers were most commonly seen in the "breathing out" steps, before and after medication inhalation. Personalized nursing educational programs, correcting errors individually for each patient, could dramatically increase the accuracy of inhaler use and the effectiveness of the inhaled medications in patients with COPD.

  20. In vitro and in vivo techniques used in drug development for evaluation of dose delivery of inhaled corticosteroids.

    PubMed

    Rhodes, G R; Rohatagi, S; Gillen, M S; Deluccia, F; Banerji, D D; Chaikin, P

    2001-01-01

    Oral inhaled corticosteroids are important in the treatment of asthma since their delivery is targeted directly to the lung, which is the site of action. Triamcinolone acetonide (TAA) is an effective and safe corticosteroid that is marketed as a metered-dose inhaler (MDI) with an integrated spacer (Azmacort) for the treatment of asthma. Due to the phasing out of chlorofluorocarbon (CFC) propellants, Azmacort has been reformulated with a non-CFC propellant. Due to the complexities of oral inhaled formulations and the topical nature of drug delivery to the lung for efficacy, the reformulation of oral inhaled MDIs requires careful consideration and support throughout their development, using a combination of in vitro and in vivo studies to ensure clinical comparability for both efficacy and safety. This paper describes a chronological series of studies designed to support the reformulation of Azmacort. These included in vitro studies to estimate respirable fraction, in vivo pulmonary deposition studies, in vivo pharmacokinetic-pharmacodynamic studies to estimate the systemic effects of each formulation, and final clinical studies in adult and pediatric patients to confirm the clinical comparability of the new formulation of Azmacort. The results of these studies, performed at various stages during the development of new formulations, were critical in guiding the reformulation efforts for Azmacort.

  1. Delivery of propellant soluble drug from a metered dose inhaler.

    PubMed Central

    Ashworth, H L; Wilson, C G; Sims, E E; Wotton, P K; Hardy, J G

    1991-01-01

    The deposition of particulate suspensions delivered from a metered dose inhaler has been investigated extensively. The distribution of propellant, delivered from a metered dose inhaler, was studied by radiolabelling it with technetium-99m hexamethylpropyleneamine oxime. Andersen sampler measurements indicated that half of the dose was associated with particles in the size range 0.5-5 microns diameter. The preparation was administered to healthy subjects by inhalation and deposition was monitored with a gamma camera. Each lung image was divided into an inner, mid, and peripheral zone. The effects on deposition of varying the size of the delivery orifice (0.46, 0.61, and 0.76 mm internal diameters) and the effect of attaching a spacer were assessed. Lung deposition was independent of the orifice size within the actuator. Without the spacer the average dose deposited in the lungs was 39%, with 15% penetrating into the peripheral part of the lungs. Attachment of the spacer to the mouth-piece increased the mean lung deposition to 57% and reduced oropharyngeal deposition. The study has shown that propellant soluble drugs can be delivered efficiently to the lungs from a metered dose inhaler. Images PMID:2038731

  2. 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.

  3. Influence of the storage orientation on the aerodynamic particle size of a suspension metered dose inhaler containing propellant HFA-227.

    PubMed

    Berry, Julianne; Kline, Lukeysha C; Hart, John L; Sequeira, Joel

    2003-07-01

    Presented in this work are the results of a study designed to investigate the impact of the storage position on the particle size distribution (PSD) of a steroid suspension metered dose inhaler (MDI) containing propellant HFA-227. It was hypothesized that the orientation of MDI samples upon storage could influence the PSD of the emitted dose, since it determines the amount of contact the liquid formulation has with the valve and therefore the quantity of nonvolatile leachable materials from the valve components that may enter the product and potentially impact the aerosol spray dynamics. Samples stored in the valve down orientation (i.e., complete contact of the liquid formulation with the valve) showed a higher level of leachables compared to those samples stored valve up (i.e., minimal contact of the formulation with the valve). The valve down samples were found to produce larger particles in the emitted aerosol spray using both cascade impaction, the preferred method of regulatory submission, as well as laser diffraction. It was postulated that the larger particle size of the inverted samples was attributed to its higher levels of leachables. Based on our findings, it is recommended that in order to set appropriate controls on the product PSD, the storage orientation of the product will need to be considered.

  4. 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.

  5. 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

  6. A method for determination of the absolute pulmonary bioavailability of inhaled drugs: Terbutaline

    SciTech Connect

    Borgstroem, L.N.; Nilsson, M. )

    1990-10-01

    Terbutaline sulfate (4 X 0.250 mg) was given to 11 healthy volunteers by inhalation from a metered dose inhaler (MDI), with and without oral administration of a charcoal slurry. Before the inhalations, the adsorbing capacity of the charcoal slurry was tested. Deuterated terbutaline, 0.125 mg, was given intravenously at the same time as the test doses. The charcoal slurry adsorbed 97% of an oral dose. The oral contribution to the overall systemic bioavailability after inhalation, when charcoal was coadministered, could thus be neglected. After inhalation of terbutaline, 9.1% of the dose was deposited in the lungs and an additional 6.7% was systemically available via the oral route. The method presented measures the absolute pulmonary bioavailability after inhalation from a MDI. Since a deuterated analogue is given intravenously together with the inhalations, fewer subjects are needed to obtain reliable data.

  7. 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.

  8. Does it really matter what volume to exhale before using asthma inhalation devices?

    PubMed

    Self, Timothy H; Pinner, Nathan A; Sowell, Rebecca S; Headley, A Stacey

    2009-04-01

    Correct use of inhalation devices is one essential component of optimal management of asthma. Several longstanding controversies regarding specific steps to correct use of metered dose inhalers (MDI) include the lung volume when the MDI should be actuated. As a primary objective, literature was reviewed examining this one step in MDI use. Results from six of nine investigations support the need to gently exhale either to functional residual capacity (FRC) or residual volume (RV) before MDI actuation. Literature is also summarized regarding the need to exhale to FRC or RV before inhaling from MDI plus valved holding chambers or other extension devices and from dry powder inhalers. Numerous studies indicate that many patients as well as health care professionals either do not know or forget to exhale to RV or FRC before inhaling asthma medications. Both patients and health care professionals need education to help ensure correct use of MDI and other asthma inhalation devices, including instruction to first exhale gently to RV or FRC before inhaling the medication.

  9. Effectiveness of Various Methods of Teaching Proper Inhaler Technique.

    PubMed

    Axtell, Samantha; Haines, Seena; Fairclough, Jamie

    2017-04-01

    To compare the effectiveness of 4 different instructional interventions in training proper inhaler technique. Randomized, noncrossover trial. Health fair and indigent clinic. Inhaler-naive adult volunteers who spoke and read English. Subjects were assigned to complete the following: (1) read a metered dose inhaler (MDI) package insert pamphlet, (2) watch a Centers for Disease Control and Prevention (CDC) video demonstrating MDI technique, (3) watch a YouTube video demonstrating MDI technique, or (4) receive direct instruction of MDI technique from a pharmacist. Inhaler use competency (completion of all 7 prespecified critical steps). Of the 72 subjects, 21 (29.2%) demonstrated competent inhaler technique. A statistically significant difference between pharmacist direct instruction and the remaining interventions, both combined ( P < .0001) and individually ( P ≤ .03), was evident. No statistically significant difference was detected among the remaining 3 intervention groups. Critical steps most frequently omitted or improperly performed were exhaling before inhalation and holding of breath after inhalation. A 2-minute pharmacist counseling session is more effective than other interventions in successfully educating patients on proper inhaler technique. Pharmacists can play a pivotal role in reducing the implications of improper inhaler use.

  10. A Review of Electronic Devices to Assess Inhaler Technique.

    PubMed

    Carpenter, Delesha M; Roberts, Courtney A; Sage, Adam J; George, Johnson; Horne, Robert

    2017-03-01

    Multiple electronic devices exist that provide feedback on the accuracy of patient inhaler technique. Our purpose is to describe the inhaler technique feedback provided by these devices, including specific technique steps measured, how feedback is displayed, target of feedback (patient, provider, researcher), and compatibility with inhaler type (metered-dose inhaler [MDI], diskus, etc.). We identified eight devices that provide feedback on inhaler technique. Only one device assessed all evidence-based MDI technique steps. Most devices provide limited real-time feedback to patients, if any feedback at all. Technologies to assess inhaler technique are advancing and hold great potential for improving patient inhaler technique. Many devices are limited in their ability to detect all evidence-based technique steps and provide real-time user-friendly feedback to patients and providers. Usability tests with patients and providers could identify ways to improve these devices to improve their utility in clinical settings.

  11. Bronchodilation with mometasone furoate/formoterol fumarate administered by metered-dose inhaler with and without a spacer in children with persistent asthma.

    PubMed

    Berger, William E; Bensch, George W; Weinstein, Steven F; Skoner, David P; Prenner, Bruce M; Shekar, Tulin; Nolte, Hendrik; Teper, Ariel A

    2014-05-01

    The bronchodilatory effect of mometasone furoate/formoterol fumarate (MF/F) administered by metered-dose inhaler (MDI) with or without a spacer has not been evaluated previously in children aged 5-11 years. This was a randomized, multicenter, placebo-controlled, single-dose, four-period crossover study. Children with persistent asthma aged 5-11 years participated in this study. Subjects used inhaled corticosteroids with/without long-acting beta-2 agonists for 12 weeks before enrollment and at screening had forced expiratory volume in 1 sec (FEV1 ) ≥70% predicted. Subjects received MF/F MDI 100/10 µg with/without spacer (AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber), F-Dry Powder Inhaler (F-DPI) 10 µg, and placebo MDI with/without spacer in separate treatment periods. The primary endpoint was FEV1 area under the curve from 0 to 12 hr (AUC0-12hr ) for the comparison of MF/F with spacer versus placebo. Secondary measurements included MF/F without spacer versus placebo, as well as MF/F with spacer versus MF/F without spacer, and F-DPI versus placebo. Analysis was performed with an analysis of covariance model for a crossover study. Data from 87 subjects were analyzed. MF/F with spacer demonstrated a larger change in mean FEV1 AUC0-12hr versus placebo (115 vs. -9 mL), with a treatment difference of 124 mL (95% CI 94-154, P < 0.001). Similarly, MF/F without spacer versus placebo resulted in a 102 mL difference in mean-adjusted FEV1 AUC0-12hr (95% CI 73-131, P < 0.001), whereas the difference between MF/F with spacer versus MF/F without spacer was 22 mL (95% CI -8 to 52, P = 0.144). The difference between F-DPI versus placebo was 106 mL (95% CI 77-135, P < 0.001). No unexpected adverse events were observed. In this trial, MF/F MDI 100/10 µg demonstrated significant bronchodilation in children aged 5-11 years regardless of the use of a spacer. No difference in bronchodilation was observed between MF/F MDI

  12. Comparison of the efficacy and safety of high doses of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in steroid-dependent adults with moderate to severe asthma.

    PubMed

    Grzelewska-Rzymowska, I; Kroczynska-Bednarek, J; Zarkovic, J

    2003-02-01

    Nebulization for the administration of high doses of inhaled corticosteroids can benefit steroid-dependent asthmatics. The objective of this double-blind, double-dummy, multicentre, randomized, parallel-group study was to compare the efficacy and safety of high-dose corticosteroids given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 2-week run-in period, 124 patients, aged 18-70 years, with moderate to severe asthma treated with high-dose inhaled steroids were randomized to one of two treatment groups for 12 weeks: beclometasone dipropionate (BDP) suspension for nebulization 3,000-4,000 microgday(-1) b.i.d. given via a nebulizer (n = 63), or BDP spray 1,500-2000 microgday(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 61). Comparable improvements over baseline, which were statistically significant in most cases, were reported at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, clinical symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was morning pulmonary expiratory flow rate (PEFR). For the intent-to-treat population, in the BDP nebulization group mean morning PEFR increased statistically significantly from 308.7 +/- 107.81 min(-1) to 3 19.2 +/- 104.01 min(-1) while in the BDP MDI group the increase was from 301.5 +/- 94.71 min(-1) to 309.3 +/- 86.71 min(-1). The two treatments were equally well tolerated.A total of 19 patients in each group reported adverse events during the treatment period, and these were generally mild-moderate in severity. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3,000-4,000 microg day(-1) given via a nebulizer and BDP spray 1,500-2,000 microg day(-1) given via an MDI plus spacer are equally effective, with an acceptable safety and tolerability profile, when used in steroid-dependent adult patients with moderate to severe asthma.

  13. In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler.

    PubMed

    Nair, Arun; Menzies, Daniel; Hopkinson, Pippa; McFarlane, Lesley; Lipworth, Brian J

    2009-02-01

    Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers. The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. Significant suppression of OUCC and EMUCC occurred from baseline

  14. The biologically effective dose in inhalation nanotoxicology.

    PubMed

    Donaldson, Ken; Schinwald, Anja; Murphy, Fiona; Cho, Wan-Seob; Duffin, Rodger; Tran, Lang; Poland, Craig

    2013-03-19

    In all branches of toxicology, the biologically effective dose (BED) is the fraction of the total dose of a toxin that actually drives any toxic effect. Knowledge of the BED has a number of applications including in building structure-activity relationships, the selection of metrics, the design of safe particles, and the determination of when a nanoparticle (NP) can be considered to be "new" for regulatory purposes. In particle toxicology, we define the BED as "the entity within any dose of particles in tissue that drives a critical pathophysiogically relevant form of toxicity (e.g., oxidative stress, inflammation, genotoxicity, or proliferation) or a process that leads to it." In conventional chemical toxicology, researchers generally use the mass as the metric to describe dose (such as mass per unit tissue or cells in culture) because of its convenience. Concentration, calculated from mass, may also figure in any description of dose. In the case of a nanoparticle dose, researchers use either the mass or the surface area. The mass of nanoparticles is not the only driver of their activity: the surfaces of insoluble particles interact with biological systems, and soluble nanoparticles can release factors that interact with these systems. Nanoparticle shape can modify activity. In this Account, we describe the current knowledge of the BED as it pertains to different NP types. Soluble toxins released by NPs represent one potential indicator of BED for wholly or partially soluble NPs composed of copper or zinc. Rapid dissolution of these NPs into their toxic ions in the acidic environment of the macrophage phagolysosome causes those ions to accumulate, which leads to lysosome destabilization and inflammation. In contrast, soluble NPs that release low toxicity ions, such as magnesium oxide NPs, are not inflammogenic. For insoluble NPs, ζ potential can serve as a BED measurement because the exposure of the particle surface to the acidic milieu of the phagolysosome and

  15. Once-daily ciclesonide via metered-dose inhaler: Similar efficacy and safety with or without a spacer.

    PubMed

    Engelstätter, Renate; Szlávik, M; Gerber, Claudia; Beck, Ekkehard

    2009-11-01

    Inhaled corticosteroids (ICS) are recommended as first-line treatment for adults and children with persistent asthma. The Global Initiative for Asthma recommends that patients taking medium- or high-dose ICS delivered by metered-dose inhalers (MDIs) should use a spacer device. This randomized, open-label, 12-week, non-inferiority study compared the efficacy and safety of ciclesonide 160microg once daily delivered via hydrofluoroalkane-MDI alone (CIC160) or with a spacer (either an AeroChamber Plus [CIC160P] or an AeroChamber MAX [CIC160M]) in patients with persistent asthma. The primary efficacy variable was change in forced expiratory volume in 1s (FEV(1)) from baseline to study end. Significant improvements in FEV(1) were observed from baseline to study end in each treatment group; least squares mean change from baseline ranged between 0.32 and 0.34L in the per-protocol (PP) analysis and similar results were observed for the intention-to-treat (ITT) analysis (p<0.0001 for all). Non-inferiority of CIC160P and CIC160M to CIC160 was observed for both PP and ITT populations (p<0.0001 [one-sided]). In all groups, daily asthma symptom scores were reduced to 0 and significant reductions were observed in rescue medication use at study end (p<0.0001 versus baseline for all). Ciclesonide was well tolerated in all groups and no cases of oral candidiasis were reported. Morning serum cortisol levels significantly increased in all groups from baseline to study end (p< or =0.0389), with no significant between-treatment differences. In patients with persistent asthma, ciclesonide was shown to have similar efficacy and tolerability when administered via MDI alone or with a spacer.

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

    PubMed

    Aswania, O; Chrystyn, H

    2001-01-01

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

  17. Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study.

    PubMed

    Scott, Shannon D; Osmond, Martin H; O'Leary, Kathy A; Graham, Ian D; Grimshaw, Jeremy; Klassen, Terry

    2009-10-13

    Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers) in pediatric emergency departments (PEDs) for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs. Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs), and respiratory therapists (RTs), and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU) categories of elements known to influence the uptake of innovations. One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway. Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study.

  18. Barriers and supports to implementation of MDI/spacer use in nine Canadian pediatric emergency departments: a qualitative study

    PubMed Central

    Scott, Shannon D; Osmond, Martin H; O'Leary, Kathy A; Graham, Ian D; Grimshaw, Jeremy; Klassen, Terry

    2009-01-01

    Background Despite recent research supporting the use of metered dose inhalers with spacer devices (MDI/spacers) in pediatric emergency departments (PEDs) for acute exacerbations of asthma, uptake of this practice has been slow. The objectives of this study were to determine the barriers and supports to implementing MDI/spacer research and to identify factors associated with early and late adoption of MDI/spacers in Canadian PEDs. Methods Using a comparative case study design, we classified nine tertiary care pediatric hospital PEDs based on their stage of implementation. Data were collected using focus group interviews with physicians, registered nurses (RNs), and respiratory therapists (RTs), and individual interviews with both patient care and medical directors at each site. Initial coding was based on the Ottawa Model of Research Use (OMRU) categories of elements known to influence the uptake of innovations. Results One hundred and fifty healthcare professionals from nine different healthcare institutions participated in this study. Lack of leadership in the form of a research champion, a lack of consensus about the benefits of MDI/spacers among staff, perceived resistance from patients/parents, and perceived increased cost and workload associated with MDI/spacer use were the most prevalent barriers to the adoption of the MDI/spacer. Common strategies used by early-adopting sites included the active participation of all professional groups in the adoption process in addition to a well-planned and executed educational component for staff, patients, and families. Early adopter sites were also more likely to have the MDI/spacer included in a clinical protocol/pathway. Conclusion Potential barriers and supports to implementation have been identified that will help EDs adopt MDI/spacer use. Future interventions intended to increase MDI/spacer use in PEDs will need to be sensitive to the barriers identified in this study. PMID:19828086

  19. Energy Efficient Monitoring of Metered Dose Inhaler Usage.

    PubMed

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

    2016-12-01

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

  20. Experimental observations of dry powder inhaler dose fluidisation.

    PubMed

    Tuley, Rob; Shrimpton, John; Jones, Matthew D; Price, Rob; Palmer, Mark; Prime, Dave

    2008-06-24

    Dry powder inhalers (DPIs) are widely used to deliver respiratory medication as a fine powder. This study investigates the physical mechanism of DPI operation, assessing the effects of geometry, inhalation and powder type on dose fluidisation. Patient inhalation through an idealised DPI was simulated as a linearly increasing pressure drop across three powder dose reservoir geometries permitting an analysis of shear and normal forces on dose evacuation. Pressure drop gradients of 3.3, 10 and 30 kPa s(-1)were applied to four powder types (glass, aluminium, and lactose 6 and 16% fines) and high speed video of each powder dose fluidisation was recorded and quantitatively analysed. Two distinct mechanisms are identified, labelled 'fracture' and 'erosion'. 'Fracture' mode occurs when the initial evacuation occurs in several large agglomerates whilst 'erosion' mode occurs gradually, with successive layers being evacuated by the high speed gas flow at the bed/gas interface. The mechanism depends on the powder type, and is independent of the reservoir geometries or pressure drop gradients tested. Both lactose powders exhibit fracture characteristics, while aluminium and glass powders fluidise as an erosion. Further analysis of the four powder types by an annular shear cell showed that the fluidisation mechanism cannot be predicted using bulk powder properties.

  1. Evaluation of proficiency in using different inhaler devices among intern doctors.

    PubMed

    Kshatriya, Ravish M; Khara, Nimit V; Paliwal, Rajiv P; Patel, Satish N

    2016-01-01

    Doctors may have deficiencies in the ability to use different inhalers, which in turn, can result in improper technique by the patients and poorly controlled asthma and chronic obstructive pulmonary disease (COPD). To evaluate intern doctors' proficiency in using various inhaler devices. Seventy interns were evaluated for their proficiency in using pressurized metered dose inhaler (pMDI), pMDI with spacer, rotahaler, turbuhaler, and nebulizer. A structured assessment sheet was scored for identification and preparation of device, administration, coordination, and skill of explanation on a scale of 0-5. Common errors such as failure to shake pMDI before use, inability to identify the empty device, inadequate breath holding, and failure to advise gargles after use were recorded. pMDI and pMDI with spacer were identified correctly by 89% and 79% of interns. Over 90% could identify rotahaler and nebulizer whereas only 9% could identify turbuhaler. 79% and 60% could prepare pMDI and pMDI with spacer appropriately. Nebulizer preparation was performed correctly by 79% and almost all interns could not prepare turbuhaler. Only one intern administered turbuhaler correctly. About half of the participants knew the correct co-ordination for pMDI and pMDI with spacer. Two interns showed proper co-ordination in using turbuhaler. None could provide correct explanation for turbuhaler usage; whereas 76% and 70% did it for nebulizer and rotahaler, respectively. Only 43% of interns remembered to shake pMDI before use. Proficiency in using different inhaler devices amongst interns is poor. It is essential to provide adequate training for inhaler devices usage to medical graduates for proper management of asthma and COPD patients by those future primary care physicians and specialists.

  2. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    PubMed

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species.

  3. In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler

    PubMed Central

    Nair, Arun; Menzies, Daniel; Hopkinson, Pippa; McFarlane, Lesley; Lipworth, Brian J

    2009-01-01

    AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P = 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P = 0.009); the Nebuchamber 57% greater suppression (P = 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. PMID:19220273

  4. Insights into spray development from metered-dose inhalers through quantitative X-ray radiography

    SciTech Connect

    Mason-Smith, Nicholas; Duke, Daniel J.; Kastengren, Alan L.; Stewart, Peter J; Traini, Daniela; Young, Paul M; Chen, Yang; Lewis, David; Soria, Julio; Edgington-Mitchell, Daniel M; Honnery, Damon R

    2016-05-01

    Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA-propelled sprays. Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 mu m. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation.

  5. [Bronchodilators via metered-dose inhaler with spacer in the pediatric emergency department: what is the dosage?].

    PubMed

    Benito Fernández, J; Trebolazabala Quirante, N; Landa Garriz, M; Mintegi Raso, S; González Díaz, C

    2006-01-01

    Bronchodilators administrated through a metered-dose inhaler (MDI) with spacer are as effective as nebulizers in the treatment of acute asthma exacerbations in childhood. However, consensus is lacking on the most suitable dosage. To assess the effectiveness of distinct salbutamol and terbutaline doses delivered via an MDI with spacer for the treatment of acute asthma in the pediatric emergency department. This was a prospective, double-blind randomized study. All consecutive children (n = 324) between 2 and 14 years of age with acute asthma exacerbations treated in the pediatric emergency department between October 1 and November 30, 2004, were included. Two treatment groups were established: one group received a number of puffs equivalent to half the child's weight (1 puff of salbutamol = 100 microg and 1 puff of terbutaline = 250 microg) and the other group received a number of puffs equivalent to one-third of the child's weight. Three hundred twenty-four episodes were studied; there were 164 children in the first group and 160 in the second. There were no significant differences between the two groups in the mean (6 SD) age (58.34 +/- 34.72 vs 66.04 +/- 36.45 months), arterial oxygen saturation (95.49 +/- 1.93 vs 95.56 +/- 1.97) or pulmonary score (4.04 +/- 1.55 vs 3.97 +/- 1.51) at recruitment and after treatment in the emergency department (arterial oxygen saturation [96.34 +/- 1.60 vs 96.18 +/- 1.77], pulmonary score [1.87 +/- 1.33 vs 1.64 +/- 1.31]). The number of doses administered (2.17 +/- 0.91 vs 2.24 +/- 1.00) and the hospitalization rate (8.56 % vs 6.87 %) were also similar in both groups. The distinct bronchodilator doses administered via an MDI with spacer showed similar effectiveness. These findings should contribute to a reevaluation of the use of high doses of bronchodilators, at least in most acute asthma exacerbations in children.

  6. Evaluation of MDI-spacer utilization and technique in caregivers of urban minority children with persistent asthma.

    PubMed

    Reznik, Marina; Silver, Ellen Johnson; Cao, Yu

    2014-03-01

    Incorrect Metered-Dose Inhaler (MDI)-spacer technique can result in decreased drug delivery to distal airways and poor asthma outcomes. There is lack of research to examine whether the caregivers utilize proper technique when applying an MDI-spacer delivery system for young minority children with persistent asthma in the United States. The objective of this study was to evaluate MDI-spacer utilization and technique among the caregivers of Bronx minority children with persistent asthma and to determine characteristics associated with correct use. We analyzed data from 169 caregivers of urban minority children with persistent asthma (aged 2-9 years). MDI-spacer device technique was assessed using a 10-step checklist derived from the national guidelines, literature and manufacturers' instructions. Based on the median MDI-technique score of six steps demonstrated accurately, caregivers were categorized as correct (seven or more) or incorrect (six or less) users. Of the 169 caregivers, 95% were mothers, mean age 32.3 years (SD 7.6), 56% were unemployed; 74% of the children were Hispanic, 87% had either "not well controlled" or "very poorly controlled" asthma, 92% had a spacer at home and 71% used it "all" or "most" of the time. Only one caregiver correctly demonstrated all 10 steps of the MDI-spacer technique. Child's having one or more asthma-related hospitalizations in the past 12 months and higher caregiver educational level were independent predictors of correct MDI-spacer technique. The caregivers of urban, minority children with persistent asthma lack proper MDI-spacer technique, suggesting the potential value of both targeted short- and long-term educational interventions.

  7. Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma.

    PubMed

    Brocklebank, D; Wright, J; Cates, C

    2001-10-20

    To determine the clinical effectiveness of pressurised metered dose inhalers (with or without spacer) compared with other hand held inhaler devices for the delivery of corticosteroids in stable asthma. Systematic review of randomised controlled trials. Cochrane Airways Group trials database (Medline, Embase, Cochrane controlled clinical trials register, and hand searching of 18 relevant journals), pharmaceutical companies, and bibliographies of included trials. All trials in children or adults with stable asthma that compared a pressurised metered dose inhaler with any other hand held inhaler device delivering the same inhaled corticosteroid. 24 randomised controlled trials were included. Significant differences were found for forced expiratory volume in one second, morning peak expiratory flow rate, and use of drugs for additional relief with dry powder inhalers. However, either these were within clinically equivalent limits or the differences were not apparent once baseline characteristics had been taken into account. No significant differences were found between pressurised metered dose inhalers and any other hand held inhaler device for the following outcomes: lung function, symptoms, bronchial hyper-reactivity, systemic bioavailability, and use of additional relief bronchodilators. No evidence was found that alternative inhaler devices (dry powder inhalers, breath actuated pressurised metered dose inhalers, or hydrofluoroalkane pressurised metered dose inhalers) are more effective than the pressurised metered dose inhalers for delivery of inhaled corticosteroids. Pressurised metered dose inhalers remain the most cost effective first line delivery devices.

  8. Comparison of the efficacy and safety of beclometasone dipropionate suspension for nebulization and beclometasone dipropionate via a metered-dose inhaler in paediatric patients with moderate to severe exacerbation of asthma.

    PubMed

    Bisca, N; Cernatescu, I; Dragomir, D; Iacomi, A; Mirceau, M; Orascanu, D

    2003-02-01

    Nebulization simplifies the administration of effective inhaled medications to young asthmatics who experience hand-to-lung co-ordination problems and inspiratory difficulties associated with metered-dose and dry-powder inhalers, respectively. The objective of this double-blind, double-dummy multicentre, randomized, parallel-group study was to compare the efficacy and safety of corticosteroids given by nebulization or metered-dose inhalation in paediatric patients with exacerbation of asthma. Following a 24-h run-in period, 151 patients, aged 6-16years, with moderate to severe exacerbation of asthma were randomized to one of two treatment groups for 4 weeks: beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. given via a nebulizer (n = 75), or BDP spray 800 microg day(-1) b.i.d. given via a metered-dose inhaler (MDI) plus spacer (BDP MDI) (n = 76). Superimposable and statistically significant improvements over baseline were noted at study end for the two treatment groups in the various efficacy parameters evaluated (pulmonary function tests, asthma symptoms scores, and the use of rescue salbutamol). The primary efficacy endpoint was the morning pulmonary expiratory flow rate (PEFR). In the BDP nebulization group, mean morning PEFR increased statistically significantly from 233.2 +/- 86.31 min(-1) to 322.0 +/- 101.81 min(-1), while in the BDP MDI group the increase was from 222.9 +/- 87.31 min(-1) to 314.9 +/- 96.61 min(-1). Moreover, an additional 4-week treatment period at half doses, completed by 26 patients, demonstrated that improvements were maintained or further enhanced. The two treatments were equally well tolerated. A total of 25 and 26 patients in the BDP nebulization and BDP MDI groups, respectively reported adverse events during the treatment period, and these were generally mild. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 1,600 microg day(-1) given via a nebulizer and

  9. 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.

  10. Telephonic Monitoring and Optimization of Inhaler Technique

    PubMed Central

    Nelson, Philip; Young, Henry N.; Knobloch, Mary Jo

    2011-01-01

    Abstract Introduction Improper inhaler technique is a common problem affecting asthma control and healthcare costs. Telephonic asthma management can increase access to care while reducing costs and hospitalizations. However, no reliable method has been established for telephonically evaluating and correcting inhaler technique. Objective The purpose of this study was to pilot test a method for assessing and correcting patient inhaler technique via telephone. Methods Participants (n=30) were adults with asthma using metered-dose inhalers (MDIs) and diskus inhalers. A pharmacist was located in one room and communicated via telephone with a participant in another room. The pharmacist telephonically assessed and taught inhaler technique. Participants were video-recorded, and videos were later examined by a second pharmacist to visually evaluate inhaler technique. Participants were assigned pre- and posteducation inhaler technique scores for the telephonic and video assessments. Scores were based on summated scales for MDI (0–9) and diskus (0–11) inhalers. Paired samples t-tests were used to compare telephone and video assessments. Results Findings indicated a significant difference between the telephone and video assessments of MDI technique (p<0.05); however, no difference was found for the diskus inhaler. Comparing pre- and posteducation inhaler technique for MDI and diskus, mean scores significantly improved from 5.7 to 7.8 (p<0.05) and from 8.5 to 10.4 (p<0.05), respectively. Conclusions The telephonic method was able to improve and detect some deficiencies in patients' inhaler technique. However, modifications and further investigation will more clearly determine the role and value of such a telephonic intervention. PMID:21943162

  11. Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction.

    PubMed

    Zar, H J; Streun, S; Levin, M; Weinberg, E G; Swingler, G H

    2007-02-01

    Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low-cost spacers in young children. To compare the response to bronchodilator treatment given via a conventional or a low-cost bottle spacer A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI-spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. 400 children, aged (median (25th-75th centile)) 12 (6-25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (-2 (-3 to -1)), oxygen saturation (0 (-1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). A low-cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways.

  12. 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

  13. Clinical benefits of cromolyn sodium aerosol (MDI) in the treatment of asthma in children.

    PubMed

    Selcow, J E; Mendelson, L M; Rosen, J P

    1989-03-01

    A double-blind, placebo-controlled study was performed to determine the efficacy and safety of cromolyn sodium (Intal) administered to children by metered dose inhaler (MDI). Prior to entry, subjects were well controlled on cromolyn sodium capsules by Spinhaler turbo-inhaler plus beta 2 agonists. An active control interval of 2 weeks on cromolyn sodium capsules was followed by a 4-week single-blind period on placebo capsules. Those subjects whose asthma worsened significantly on placebo entered a 10-week double-blind phase, randomized to receive either cromolyn sodium (2 mg per dose) or placebo by MDI. Diary data, physician evaluation, and pulmonary function tests were used to assess efficacy, and scores were compared with the baseline value at 2-week intervals. Forty children with asthma, 8 to 20 years of age, entered the study and 32 qualified for the randomized phase. No significant differences existed between the treatment groups at baseline. Most comparative data favored the cromolyn sodium group over the course of the study. Significant differences (p less than .05) were noted for diary scores of breathlessness and overall asthma severity. There was significant improvement at the final visit favoring the cromolyn sodium group in restriction on normal activity, FEV1, and PEFR. The cromolyn sodium group also experienced a decreasing need for concomitant bronchodilators. Both groups preferred pressurized aerosol by MDI over powdered capsules by Spinhaler. (Intal and Spinhaler are registered trademarks of Fisons Corporation.)

  14. 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

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

    2016-01-01

    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. 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. 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. 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 during exacerbations, with a potential for

  15. Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD.

    PubMed

    Kilfeather, S A; Ponitz, H H; Beck, E; Schmidt, P; Lee, A; Bowen, I; Hesse, Ch

    2004-05-01

    We performed a multicentre, randomised, double-blind (within-device), placebo- and active-controlled, parallel-group study to compare the efficacy and safety of ipratropium bromide plus fenoterol hydrobromide (IB/FEN; Berodual) delivered via the novel, propellant-free Respimat Soft Mist Inhaler (SMI) and from a chlorofluorocarbon (CFC)-metered-dose inhaler (MDI) in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. After 2-weeks' run-in (CFC-MDI [IB 20 microg/FEN 50 microg per actuation] two actuations q.i.d. [MDI 40/100]), 892 patients were randomised to Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB 20 microg/FEN 50 microg (Respimat SMI 20/50) or placebo (one actuation q.i.d.), or a CFC-MDI containing IB 20 microg/FEN 50 microg (MDI 40/100) or placebo (two actuations q.i.d.) for 12 weeks. Analysis of the primary endpoint (change in forced expiratory volume in 1 s [FEV1] in the first 60 min after dosing [area under the curve; AUC0-1h]) on day 85 showed that the efficacy of Respimat SMI 20/50 (but not Respimat SMI 10/25) was not inferior to that of MDI 40/100. The safety profile of Respimat SMI was comparable to CFC-MDI. Switching from MDI 40/100 to Respimat SMI was well tolerated. Respimat SMI enables a 50% reduction of the nominal inhaled dose of IB/FEN in COPD patients while offering similar therapeutic efficacy and safety to the CFC-MDI.

  16. Use of simulated patient approach to assess the community pharmacists’ knowledge of appropriate use of metered dose inhaler

    PubMed Central

    Nduka, Sunday O.; Anetoh, Maureen U.; Amorha, Kosisochi C.; Henry, Okechukwu O.; Okonta, Mathew J.

    2016-01-01

    Rationale: The pharmacist charged with the responsibility of drug administration and counseling should have the basic knowledge and skills necessary to demonstrate the use of metered dose inhalers (MDIs) to asthma patients for the maximization of treatment outcomes. Objective: This study was designed to evaluate the community pharmacists’ knowledge of the appropriate use of MDIs in Anambra State, Nigeria. Methods: The study was carried out in two major cities in Anambra State, Nigeria, using 41 registered community pharmacists. A simulated patient approach utilizing two adequately trained pharmacy students were used. Obtained data were analyzed using independent t-test and one-way ANOVA through SPSS version 18. Results: The pharmacists had a mean demonstration score of 45.45%. Step number seven of the correct use of MDI, which involves breathing in and depressing the canister was the most demonstrated step (90.2%) while step 4 which involves tilting the head back slightly was the least demonstrated (14.6%) by the pharmacists. Among five identified critical steps in asthma guideline used, two were well demonstrated (75.6% and 90.2%): one averagely demonstrated (51.2%) and two poorly demonstrated (39% and 31.7%). Sociodemographic characteristics did not influence the demonstration ability of the pharmacists in this study. Conclusion: The study indicated that community pharmacists lacked the adequate knowledge of appropriate use of MDI. Training programs for pharmacists focusing on the use of such devices will enable them to educate patients on the effective use of MDIs in patients with asthma. PMID:27999471

  17. 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.

  18. An experimental investigation of the spray issued from a pMDI using laser diagnostic techniques.

    PubMed

    Dunbar, C A; Watkins, A P; Miller, J F

    1997-01-01

    This research was concerned with the experimental investigation of the spray issued from a pressurised metered-dose inhaler (pMDI) using laser diagnostic techniques and has been motivated by the urgent need to find suitable replacements to the environmentally destructive CFC propellants currently used in the device. The experimental work was conducted using phase-Doppler particle analysis (PDPA), a single particle light scattering technique that provides the simultaneous measurement of drop size, velocity, and concentration, yielding the most detailed temporal and spatial analysis of the pMDI spray to date. Three formulations were studied to compare the performance of an "ozone-friendly" hydrofluoroalkane propellant against that of a traditional CFC propellant mixture and a commercially available CFC formulation containing drug and surfactant. The PDPA analysis was complemented by a visual investigation of the near-orifice flow field using copper laserstrobe microcinematography to obtain information on the primary atomization process of the pMDI. This work was conducted in parallel with the theoretical investigation of the spray issued from a pMDI.

  19. Pharmacokinetic Comparison of a Unit Dose Dry Powder Inhaler with a Multidose Dry Powder Inhaler for Delivery of Fluticasone Furoate.

    PubMed

    Mehta, Rashmi; Moore, Alison; Riddell, Kylie; Joshi, Shashidhar; Chan, Robert

    2017-05-02

    The unit dose dry powder inhaler (UD-DPI) is being considered as an alternative inhaler platform that, if developed, has the potential to improve access to inhaled respiratory medicines in developing countries. This study compared the systemic exposure of fluticasone furoate after delivery from the UD-DPI with that from the ELLIPTA(®) inhaler. This open-label, five-way cross-over, randomized, single-dose study in healthy subjects evaluated fluticasone furoate systemic exposure of three dose strengths (using four inhalations), 4 × 80 μg [320 μg], 4 × 100 μg [400 μg], and 4 × 140 μg [560 μg]), and two percentages of drug in lactose blends (0.6% and 0.8% by weight) after delivery from the UD-DPI compared with systemic exposures from the ELLIPTA inhaler (4 × 100 μg [400 μg] dose, 0.8% lactose blend). The primary treatment comparisons were area under the concentration-time curve from time 0 to 6 hours [AUC0-6] and maximum plasma concentration [Cmax]. After single-dose administration of fluticasone furoate, systemic exposure was lower from all UD-DPI formulations versus the ELLIPTA inhaler in terms of both AUC0-6 [AUC0-6 geometric least squares mean (GLM) ratios confidence interval (90% CI) for: UD-DPI (400 μg 0.8% blend)/ELLIPTA: 0.61 (0.55-0.67) and Cmax GLM (90% CI) for: UD-DPI (400 μg 0.8% blend)/ELLIPTA: 0.56 (0.49-0.64)]. Systemic exposures were ∼10% lower for fluticasone furoate UD-DPI for the 0.8% blend versus the 0.6% blend [GLM ratio (90% CI); 0.90 (0.81-1.00) for AUC0-6 and 0.89 (0.77-1.01) for Cmax], and increasing doses of fluticasone furoate from the UD-DPI showed systemic exposures that were approximately dose proportional. All treatments were well tolerated. Fluticasone furoate systemic exposure was lower from the UD-DPI than from the ELLIPTA inhaler, but the UD-DPI formulations did demonstrate detectable systemic levels and approximate dose proportionality. Together with the good tolerability shown

  20. Study of Proper use of Inhalational Devices by Bronchial Asthma or COPD Patients Attending a Tertiary Care Hospital

    PubMed Central

    Das, Anup Kumar; Roy, Anindya; Adhikari, Anjan; Banerjee, Joyashree; Sen, Sumitra

    2014-01-01

    Objective: To examine the frequency of proper use of inhalation devices and influence of age and training on it. Materials and Methods: One hundred and five subjects of bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD); aged between 18 to 75 y (mean ± SD; 46 ± 28.55) were studied. Subjects were enrolled over a period of three months. Data like weight, height and concomitant medications were recorded. It was an observational and questionnaire based study. Parameters were chosen to demonstrate the inhalational technique, errors committed in different steps of use & nature of medical, paramedical, nursing personals and others imparting training for use of inhaler device and time devoted for it. Results: Of total 105 patients, 31 were using dry powdered inhalers (DPI), 50 on metered dose inhalers (MDI), and 24 on MDI with spacer devices. Among study population 83.81% were trained by healthcare professionals (doctors, nurse, pharmacists, paramedical or representatives of Pharmaceutical companies) and 16.19% are trained by general people. Among the MDI users (n=50) only 6%, 16.12% among the DPI users, 20.8%, among MDI with spacer users could use inhalers correctly. At 95% confidence limit there was significance of errors committed between DPI and MDI users (difference of SE is 2.56) and between spacer and MDI users (difference of SE 2.92). There was no difference found in regard of frequency of errors committed in taking different devices according to patient’s socioeconomic, educational background and trainer. Conclusion: It was concluded that use of MDI with spacer most convenient method. Doctors often did not have sufficient time to train patients regarding proper technique of inhaler use. With ever increasing and widespread use of inhalers patients’ education is becoming more important. Proper training will surely make these drugs more effective and cost benefit ratio more favourable. PMID:25478367

  1. The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study.

    PubMed

    Jones, Rupert; Martin, Jessica; Thomas, Vicky; Skinner, Derek; Marshall, Jonathan; Stagno d'Alcontres, Martina; Price, David

    2017-01-01

    Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 μg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 μg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 μg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI.

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

    SciTech Connect

    Hanna, L.M.

    1993-01-01

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

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

    PubMed

    Anderson, Paula

    2006-01-01

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

  4. Safety and Efficacy of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler Compared with Fluticasone Propionate/Salmeterol Diskus in Patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Koser, Andras; Westerman, Jan; Sharma, Sanjay; Emmett, Amanda; Crater, Glenn D

    2010-01-01

    Purpose: To provide information on the efficacy and safety of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler 230/42mcg (FSC MDI) and its comparable dose of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg (FSC DISKUS) in patients with COPD. Methods: This multicenter, randomized, double-blind, 12 week study was designed to evaluate FSC MDI treatment responses as compared with FSC DISKUS. The primary comparison of interest was non-inferiority between the FSC MDI treatment group and the FSC DISKUS treatment group assessed in terms of 2-hour post-dose FEV1 change from baseline at endpoint. The non-inferiority criterion bound was 75mL (lower confidence limit of -75mL). Inclusion criteria: Male or female aged ≥ 40, post-bronchodilator FEV1 ≤ 70% predicted normal, FEV1/FVC ≤ 70% and ≥ 10 pack years smoking history. Adverse events were recorded by patients throughout the study on daily diary cards. Adverse events were collected in eCRFs at all clinic visits and during a final follow-up phone call. Results: Patients (N=247) were randomized to FSC MDI (FEV1% 49.3 ± 12.3, FEV1/FVC 50.5 ± 10.0) and FSC DISKUS (FEV1% 48.4 ± 11.0, FEV1/FVC 50.3 ± 10.3). From an ANCOVA model the least squares (LS) mean difference (FSC MDI– FSC DISKUS) for the 2-hour post dose FEV1 at endpoint was -2.0mL (95% CI -64mL, 59mL). Pre-dose FEV1, FVC, PEF, and albuterol use were also similar between the two formulations. The most common adverse events (AE) during treatment were headache (8% and 6% of patients), nasopharyngitis (4% and 6%), cough (3% and 4%), and sinusitis (2% and 5%) for FSC MDI and FSC DISKUS, respectively. Pneumonia was recorded as an AE for 2 (2%) patients in the FSC DISKUS arm. Conclusion: This is the first study to demonstrate that FSC MDI has a similar efficacy and safety profile to FSC DISKUS in COPD patients. PMID:21253451

  5. Reconstruction of the inhalation dose in the 30-km zone after the Chernobyl accident.

    PubMed

    Mück, Konrad; Pröhl, Gerhard; Likhtarev, Ilya; Kovgan, Lina; Golikov, Vladislav; Zeger, Johann

    2002-02-01

    Due to lack of measurements of activity concentrations in air, the assessment of the inhalation dose of the population evacuated from the 30-km zone after the Chernobyl accident is not possible from continuous filter measurements. Since the evaluation of the inhalation dose in each settlement of the zone is of great interest for epidemiological purposes, an approach was chosen that utilizes the available data on ground deposition of 137Cs, a recently performed best estimate of the radionuclide vector and its spatial distribution as well as the radionuclide dependent deposition velocity. The derived inhalation dose values in the 30-km zone range between 3 mSv to 150 mSv effective dose for adults depending on the distance to the reactor site and the day of evacuation. For 1-y-old infants the values range between 10 to 700 mSv. In Chernobyl town, an effective inhalation dose of 25 mSv until evacuation day was assessed. Thyroid doses due to inhalation ranged from 0.02 to 1 Sv for adults, for 1-y-old infants from 0.02 to 6 Sv. The inhalation dose in each settlement of the 30-km zone is approximately 8-13 times higher than the external exposure in each settlement if evacuation of the settlement occurred at an early stage. For settlements with evacuation at a later stage (day 10 or later) the inhalation dose was about 50-70% higher than the external dose. The dominant contribution to the effective inhalation dose comes from 131I (about 40%) and tellurium and rubidium isotopes (about 20-30%). Despite high zirconium and cerium ground depositions, zirconium and cerium isotopes contribute rather little to the inhalation dose which is mainly due to the great particle sizes to which they are attached. The relative contribution of short-lived radionuclides is, despite higher activities than at greater distances, less than 5%.

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

    PubMed

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

    2005-01-01

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

  7. Predictors of incorrect inhalation technique in patients with asthma or COPD: a study using a validated videotaped scoring method.

    PubMed

    Rootmensen, Geert N; van Keimpema, Anton R J; Jansen, Henk M; de Haan, Rob J

    2010-10-01

    Inadequate technique reduces the effects of inhalation medication. Errors in inhalation technique have been reported to range up to 85%. Not only various patients' characteristics but also the device has an effect on correct inhalation technique. The purpose of this study was to determine the effect of patients' characteristics and type of inhaler device on inhalation technique in patient with asthma or chronic obstructive pulmonary disease (COPD). A validated scoring method was used that consisted of triple viewing of video-recorded inhalations, using device-specific checklists. The following patient characteristics were investigated: gender, age, education level, diagnosis, treatment by a pulmonary physician, previously received inhalation instruction, exacerbation frequency, knowledge, self-management competence, pulmonary function, and use of multiple inhaler devices. Chi-square statistics were used for univariate associations between potential determinants and correctness of inhalation technique. Relevant determinants were entered into a multivariate logistic regression model. Moreover, inhalation technique errors were examined for six inhaler devices: three prefilled dry powder inhalers, one single-dose dry powder inhaler, a pressurized metered-dose inhaler (pMDI) and a pMDI with a spacer. Overall, 40% of the patients made at least one essential mistake in their inhalation technique. Patients who never received inhalation instruction and patients who used more than one inhaler device made significantly more errors (odds ratio both 2.2). Comparison between devices showed that a correct inhalation technique most likely occurred with the use of prefilled dry powder devices. Incorrect inhalation technique is common among asthma and COPD patients in a pulmonary outpatient clinic. Our study suggests that the use of prefilled dry powder inhalers as well as inhalation instruction increases correct inhalation technique. Simultaneous use of different types of

  8. Multiple dose pharmacokinetics of inhaled loxapine in subjects on chronic, stable antipsychotic regimens

    PubMed Central

    Riesenberg, Robert A.; Cassella, James V.

    2015-01-01

    Abstract This randomized, double‐blind, placebo‐controlled, parallel‐group study was to determine the pharmacokinetic characteristics, safety, and tolerability of multiple doses of inhaled loxapine aerosol in subjects on a stable, oral, chronic antipsychotic regimen. Loxapine was delivered by means of a unique thermally generated aerosol comprising drug particles of a size designed for deep lung delivery and absorption. Thirty‐two subjects were randomized 1:1:1:1 to receive inhaled loxapine (total doses of 15, 20, or 30 mg) or inhaled placebo administered in 3 divided doses, given 4 hours apart. Following inhalation, the median Tmax was 2 minutes, and concentrations declined to about half Cmax approximately 5 minutes later across the 3 dose levels. The dose proportionality across data from this study combined with data from the single‐dose study showed a slope (90%CI) of log AUCinf versus log dose of 0.818 (0.762–0.875) across the 8 doses (n = 60 subjects) studied, indicating reasonable dose proportionality. The most common adverse events were cough (3 of 32, 9%), sedation (3 of 32, 9%), and dysgeusia (2 of 32, 6%). The inhalation of multiple doses of inhaled loxapine were well tolerated in study subjects and provided a safe, well‐tolerated means for rapidly and reliably achieving therapeutic plasma concentrations of loxapine. ClinicalTrials.gov identifier: NCT00555412 PMID:25808074

  9. Evaluation of the TSI aerosol impactor 3306/3321 system using a redesigned impactor stage with solution and suspension metered-dose inhalers.

    PubMed

    Harris, Julie A; Stein, Stephen W; Myrdal, Paul B

    2006-03-01

    The purpose of this research was to evaluate a redesigned impactor stage for the TSI Model 3306 Impactor Inlet with nozzles adjusted to obtain a target cut-point of 4.7 μm. It has been determined that the previous cut-point used in the Model 3306 was nominally closer to 4.14 μm, thus potentially impacting the characterization of aerosol mass. The reassessment of the Model 3306 was performed on 4 solution and 2 suspension metered-dose inhaler (MDI) formulations. The redesigned impactor stage resulted in a 5% to 6% increase in aerosol mass when compared with the previous impactor stage for the products Ventolin-HFA, Proventil-HFA, and 2 cyclosporin solution formulations with high ethanol concentrations (15% wt/wt). For the formulations with low ethanol concentrations (3% wt/wt), minimal differences were observed between the 2 cut-points. In addition, this study reevaluated the requirement of a vertical inlet extension length when using the TSI 3306/3321 system with the redesigned cut-point. It was shown that the use of a 20-cm extension provides mass and aerosol size distributions that are comparable to the Andersen 8-stage Cascade Impactor, for both solution and suspension MDIs. This work indicates that the TSI 3306/3321 system is suitable for preformulation studies of both suspension and solution MDI systems.

  10. Evaluation of the TSI aerosol impactor 3306/3321 system using a redesigned impactor stage with solution and suspension metered-dose inhalers.

    PubMed

    Harris, Julie A; Stein, Stephen W; Myrdal, Paul B

    2006-03-10

    The purpose of this research was to evaluate a redesigned impactor stage for the TSI Model 3306 Impactor Inlet with nozzles adjusted to obtain a target cut-point of 4.7 microm. It has been determined that the previous cut-point used in the Model 3306 was nominally closer to 4.14 microm, thus potentially impacting the characterization of aerosol mass. The reassessment of the Model 3306 was performed on 4 solution and 2 suspension metered-dose inhaler (MDI) formulations. The redesigned impactor stage resulted in a 5% to 6% increase in aerosol mass when compared with the previous impactor stage for the products Ventolin-HFA, Proventil-HFA, and 2 cyclosporin solution formulations with high ethanol concentrations (15% wt/wt). For the formulations with low ethanol concentrations (3% wt/wt), minimal differences were observed between the 2 cut-points. In addition, this study reevaluated the requirement of a vertical inlet extension length when using the TSI 3306/3321 system with the redesigned cut-point. It was shown that the use of a 20-cm extension provides mass and aerosol size distributions that are comparable to the Andersen 8-stage Cascade Impactor, for both solution and suspension MDIs. This work indicates that the TSI 3306/3321 system is suitable for preformulation studies of both suspension and solution MDI systems.

  11. Inhalants

    MedlinePlus

    ... Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids ... Cold Medicine Abuse Electronic Cigarettes (E-cigarettes) Fentanyl Hallucinogens Heroin Inhalants Marijuana Marijuana as Medicine MDMA (Ecstasy/ ...

  12. Inhalants

    MedlinePlus

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

  13. 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 ...

  14. Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering β2 agonists bronchodilators in asthma

    PubMed Central

    Ram, Felix S F; Wright, John; Brocklebank, David; White, John E S

    2001-01-01

    Objectives To determine the clinical effectiveness of pressurised metered dose inhalers compared with other hand held inhaler devices for delivering short acting β2 agonists in stable asthma. Design Systematic review of randomised controlled trials. Data sources Cochrane Airways Group specialised trials database (which includes hand searching of 20 relevant journals), Medline, Embase, Cochrane controlled clinical trials register, pharmaceutical companies, and bibliographies of included trials. Trials All trials in children or adults with stable asthma that compared the pressurised metered dose inhaler (with or without a spacer device) against any other hand held inhaler device containing the same β2 agonist. Results 84 randomised controlled trials were included. No differences were found between the pressurised metered dose inhaler and any other hand held inhaler device for lung function, blood pressure, symptoms, bronchial hyperreactivity, systemic bioavailability, inhaled steroid requirement, serum potassium concentration, and use of additional relief bronchodilators. In adults, pulse rate was lower in those using the pressurised metered dose inhaler compared with those using Turbohaler (standardised mean difference 0.44, 95% confidence interval 0.05 to 0.84); patients preferred the pressurised metered dose inhaler to the Rotahaler (relative risk 0.53, 95% confidence interval 0.36 to 0.78); hydrofluoroalkane pressurised metered dose inhalers reduced the requirement for rescue short course oral steroids (relative risk 0.67, 0.49 to 0.91). Conclusions No evidence was found to show that alternative inhaler devices are more effective than standard pressurised metered dose inhalers for delivering acting β2 agonist bronchodilators in asthma. Pressurised metered dose inhalers remain the most cost effective delivery devices. What is already known on this topicMany different inhaler devices are available for administration of short acting β2 agonists in asthma

  15. Improving asthma management: the case for mandatory inclusion of dose counters on all rescue bronchodilators.

    PubMed

    Conner, Jill B; Buck, Philip O

    2013-08-01

    Asthma remains a serious global health challenge. Poor control of asthma symptoms is due in part to incorrect use of oral inhaler devices that deliver asthma medications, such as poor inhalation technique or use of a metered dose inhaler (MDI) after the recommended number of doses is expelled. To review published research on the potential for patients to overestimate or underestimate the amount of asthma rescue medication in MDIs without integrated dose-counting mechanisms. We searched PubMed and EMBASE using search terms "dose counter and asthma" and "dose counter and metered dose inhaler" for English language publications up to July, 2012, with a manual search of references from relevant articles. Up to 40% of patients believe they are taking their asthma medication when they actually are activating an empty or nearly empty MDI. Device design makes it impossible for an MDI to cease delivering drug doses at an exact point, and the number of actuations in an MDI may be twice the nominal number of recommended medication doses. Once the recommended number of medication doses is expelled, remaining actuations deliver decreasing concentrations of active medication and increasing concentrations of propellants and excipients. This phenomenon, called "tail-off," is particularly problematic when medications are formulated as suspensions, as are rescue medications to control acute bronchospasm. Reliable inhalation of rescue medication could reduce asthma-related morbidity. By helping to ensure that patients receive accurate metered doses of asthma rescue medication to relieve bronchoconstriction, dose counters may help to improve asthma management.

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

    PubMed

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

    2003-03-01

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

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

    PubMed Central

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

    2003-01-01

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

  18. Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering beta (2 )agonists bronchodilators in asthma.

    PubMed

    Ram, F S; Wright, J; Brocklebank, D; White, J E

    2001-10-20

    To determine the clinical effectiveness of pressurised metered dose inhalers compared with other hand held inhaler devices for delivering short acting beta(2) agonists in stable asthma. Systematic review of randomised controlled trials. Cochrane Airways Group specialised trials database (which includes hand searching of 20 relevant journals), Medline, Embase, Cochrane controlled clinical trials register, pharmaceutical companies, and bibliographies of included trials. All trials in children or adults with stable asthma that compared the pressurised metered dose inhaler (with or without a spacer device) against any other hand held inhaler device containing the same beta(2) agonist. 84 randomised controlled trials were included. No differences were found between the pressurised metered dose inhaler and any other hand held inhaler device for lung function, blood pressure, symptoms, bronchial hyperreactivity, systemic bioavailability, inhaled steroid requirement, serum potassium concentration, and use of additional relief bronchodilators. In adults, pulse rate was lower in those using the pressurised metered dose inhaler compared with those using Turbohaler (standardised mean difference 0.44, 95% confidence interval 0.05 to 0.84); patients preferred the pressurised metered dose inhaler to the Rotahaler (relative risk 0.53, 95% confidence interval 0.36 to 0.78); hydrofluoroalkane pressurised metered dose inhalers reduced the requirement for rescue short course oral steroids (relative risk 0.67, 0.49 to 0.91). No evidence was found to show that alternative inhaler devices are more effective than standard pressurised metered dose inhalers for delivering acting beta(2 )agonist bronchodilators in asthma. Pressurised metered dose inhalers remain the most cost effective delivery devices.

  19. A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration.

    PubMed

    Argenti, D; Shah, B; Heald, D

    2000-05-01

    The impending phaseout of chlorofluorocarbons as propellants in pressurized metered-dose inhalers used in the treatment of asthma has resulted in the development of alternative devices to deliver drug to the pulmonary airways. These alternative devices include metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated dry-powder inhalers. The purpose of this study was to compare the single- and multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide (Azmacort HFA 225 mcg Inhalation Aerosol) to that of the dry-powder formulation of budesonide (Pulmicort Turbuhaler 200 mcg). This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide, 600 mcg dose of budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum cortisol, 24-hour overnight serum cortisol AUC(0-24), and 24-hour urinary-free cortisol after the last evening dose of test drug. Tolerability was assessed through physical examinations, vital signs, 12-lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24-hour serum cortisol AUC(0-24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.

  20. A Tablet-Based Multimedia Education Tool Improves Provider and Subject Knowledge of Inhaler Use Techniques.

    PubMed

    Mulhall, Aaron M; Zafar, Muhammad A; Record, Samantha; Channell, Herman; Panos, Ralph J

    2017-02-01

    Although inhaled medications are effective therapies for COPD, many patients and providers use them incorrectly. We recruited providers who prescribe inhalers or teach inhaler technique and assessed their use of metered-dose inhalers (MDIs), various dry powder inhalers (DPIs), and Respimat using predefined checklists. Then they watched tablet-based multimedia educational videos that demonstrated correct inhaler technique by a clinical pharmacist with teach-back from a patient and were re-evaluated. We also recruited patients with COPD and assessed their use of their prescribed inhalers and then retested them after 3-6 months. Baseline and follow-up respiratory symptoms were measured by the COPD Assessment Test. Fifty-eight providers and 50 subjects participated. For all providers, correct inhaler technique (reported as percentage correct steps) increased after the videos: MDI without a spacer (72% vs 97%) MDI with a spacer (72% vs 96%), formoterol DPI (50% vs 94%), mometasone DPI (43% vs 95%), tiotropium DPI (73% vs 99%), and Respimat (32% vs 93%) (before vs after, P < .001 for all comparisons). Subjects also improved their inhaler use technique after viewing the educational videos: MDI without a spacer (69% vs 92%), MDI with a spacer (73% vs 95%), and tiotropium DPI (83% vs 96%) (before vs after, P < .001 for all comparisons). The beneficial effect of this educational intervention declined slightly for subjects but was durably improved after several months. COPD Assessment Test scores did not demonstrate any change in respiratory symptoms. A tablet-based inhaler education tool improved inhaler technique for both providers and subjects. Although this intervention did show durable efficacy for improving inhaler use by patients, it did not reduce their respiratory symptoms. Copyright © 2017 by Daedalus Enterprises.

  1. 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...

  2. 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...

  3. Randomised controlled trial of the efficacy of a metered dose inhaler with bottle spacer for bronchodilator treatment in acute lower airway obstruction

    PubMed Central

    Zar, H J; Streun, S; Levin, M; Weinberg, E G

    2007-01-01

    Background Inhaled bronchodilator treatment given via a metered dose inhaler (MDI) and spacer is optimal for relief of bronchoconstriction. Conventional spacers are expensive or unavailable in developing countries, but there is little information on the efficacy of low‐cost spacers in young children. Objective To compare the response to bronchodilator treatment given via a conventional or a low‐cost bottle spacer Methods A randomised controlled trial of the efficacy of a conventional spacer compared with a bottle spacer for bronchodilator treatment in young children with acute lower airway obstruction. Bronchodilator treatment was given from an MDI via an Aerochamber or a bottle spacer. Clinical score and oximetry recording were carried out before and after 15 min of treatment. MDI–spacer treatment was repeated up to three times, depending on clinical response, after which nebulisation was used. The primary outcome was hospitalisation. Results 400 children, aged (median (25th–75th centile)) 12 (6–25) months, were enrolled. The number of children hospitalised (n = 60, 15%) was identical in the conventional and bottle spacer groups (n = 30, 15% in each). Secondary outcomes including change in clinical score (−2 (−3 to −1)), oxygen saturation (0 (−1 to 1)) and number of bronchodilator treatments (2 (1 to 3)) were similar in both groups. Oral corticosteroids, prescribed for 78 (19.5%) children, were given to a similar number in the conventional (37 (18.5%)) and bottle spacer groups (41 (20.5%)). Conclusion A low‐cost bottle spacer is as effective as a conventional spacer for bronchodilator treatment in young children with acute obstruction of the lower airways. PMID:16905564

  4. Deposition and pharmacokinetics of flunisolide delivered from pressurized inhalers containing non-CFC and CFC propellants.

    PubMed

    Richards, J; Hirst, P; Pitcairn, G; Mahashabde, S; Abramowitz, W; Nolting, A; Newman, S P

    2001-01-01

    Our objective was to assess the deposition and pharmacokinetics of a novel formulation of flunisolide (Aerobid, Forest Laboratories) in hydrofluoroalkane (HFA) 134a delivered by pressurized metered dose inhaler (pMDI). The design was a two-way crossover investigation in 12 healthy male subjects comparing HFA-134a flunisolide by pMDI versus pMDI plus 50 mL spacer device. Four of these subjects also took part in a two-way crossover investigation comparing chlorofluorocarbon (CFC) flunisolide pMDI versus pMDI plus Aerochamber holding chamber. The imaging technique of gamma scintigraphy was used to quantify total and regional lung deposition of flunisolide. Plasma levels of flunisolide and its major metabolite (6beta-OH flunisolide) were also determined. The spacer and Aerochamber reduced oropharyngeal deposition dramatically for both the HFA and CFC products (mean 59.8 to 14.9% (p < 0.01) of ex-valve (metered) dose for HFA product; 66.3 to 12.3% (p < 0.01) of ex-valve dose for CFC product) owing to deposition of part of the dose on the walls of the add-on devices themselves. Lung deposition averaged 22.6 and 40.4% (p < 0.01) of the ex-valve dose for the HFA formulation used with pMDI alone and with pMDI plus spacer. Mean lung deposition of the CFC formulation delivered via the Aerochamber (mean 23.4%) was higher than that for the CFC pMDI alone (mean 17.0%), but this difference was not statistically significant. Lung deposition expressed as percentage ex-device (delivered) dose averaged 68.3% for HFA pMDI plus spacer and 19.7% for CFC pMDI. Plasma levels of flunisolide were higher for the pMDI plus spacer than for pMDI alone, reflecting higher lung deposition via the spacer, but plasma levels of the 6beta-OH flunisolide metabolite were higher for the pMDI alone as a consequence of higher oropharyngeal deposition. When delivered via the spacer, pulmonary targeting of the flunisolide HFA formulation was improved compared with the CFC formulation, which should benefit

  5. 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

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

    PubMed

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

    2015-09-01

    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. 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. 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. 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. © 2015 The British Pharmacological Society.

  7. Dose-response relationships of inhaled insulin delivered via the Aerodose insulin inhaler and subcutaneously injected insulin in patients with type 2 diabetes.

    PubMed

    Kim, Dennis; Mudaliar, Sunder; Chinnapongse, Sithipol; Chu, Neelima; Boies, Sarah M; Davis, Trent; Perera, Ayesh D; Fishman, Robert S; Shapiro, David A; Henry, Robert

    2003-10-01

    To compare the dose-response relationship following inhalation of regular insulin delivered via the Aerodose insulin inhaler with that following subcutaneously injected regular insulin in patients with type 2 diabetes. Twenty-four patients with type 2 diabetes (21 nonsmoking men, aged 36-80 years) each received two of three doses of 80, 160, or 240 units inhaled regular insulin, delivered via a clinical Aerodose insulin inhaler, and two of three corresponding doses of 8, 16, or 24 units by subcutaneous injection under isoglycemic clamp conditions on 4 separate study days in an incomplete block design study. Glucose infusion rates (GIRs) and serum insulin concentrations were monitored over the following 8 h. Inhaled insulin exhibited significantly shorter time-to-peak insulin levels (T(max) 77 +/- 66 vs. 193 +/- 104 min, P < 0.001) and time-to-peak metabolic effects (T(GIRmax) 240 +/- 94 vs. 353 +/- 60 min, P < 0.001) compared with subcutaneously injected insulin. Comparison of total insulin absorption (insulin area under the curve [AUC]) versus total metabolic effect (GIR-AUC) from 0 to 8 h (group means) revealed overlapping dose-response relationships for both inhaled and subcutaneous injection treatments. Comparison of slopes revealed no significant differences between the inhaled and subcutaneous injection treatment groups (P = 0.6). No significant differences in either relative bioavailability or relative biopotency were found among doses, indicating a consistent subcutaneous injection-to-inhaled dosing conversion ratio among doses. No serious adverse events or clinically relevant changes in lung function were observed. The overlapping dose-response curves of inhaled and subcutaneous treatments together with a consistent relative bioavailability and relative biopotency for inhaled insulin across doses suggest that the Aerodose insulin inhaler will deliver a pharmacologically predictable insulin dose to patients with diabetes similar to that observed following

  8. The Effect of Training Inhalation Technique with or without Spacer on Maximum Expiratory Flow Rate and Inhaler Usage Skills in Asthmatic Patients: A Randomized Controlled Trial.

    PubMed

    Rahmati, Hashem; Ansarfard, Fatemeh; Ghodsbin, Fariba; Ghayumi, Mohammad Ali; Sayadi, Mehrab

    2014-10-01

    The most common treatment for asthma is transferring the drug into the lungs by inhaler devices. Besides, correct use of inhaled medication is required for effectiveness of pharmacotherapy. Thus, it is necessary to train the patients how to use Metered Dose Inhaler (MDI). This study aimed to determine the effect of training about MDI usage with or without spacer on maximum expiratory flow rate and inhaler usage skills in asthmatic patients. This randomized clinical trial was conducted on 90 asthmatic patients who were randomly divided into inhalation technique group with spacer, inhalation technique group without spacer, and a control group. Then, the Peak Expiratory Flow Rate (PEFR) was measured using a peak flow meter, as a basic test. In addition, the patients' functional skills of inhalation technique were assessed using two checklists. Afterwards, 3 sessions of training were arranged for both groups. PEFR and the ability to use the MDI were evaluated immediately and 1 month after the intervention. Finally, the data were entered into the SPSS statistical software (v. 18) and analyzed using independent t-test and repeated measures ANOVA. After the intervention, MDI usage skills improved in the two intervention groups compared to the control group (P<0.001). In addition, a significant difference was found between the intervention groups and the control group regarding the mean of PEFR after the intervention (P<0.001). However, no significant difference was observed between the two intervention groups (P=0.556). According to the results, providing appropriate training for asthmatic patients increased MDI usage skills, and both methods of inhalation (with or without spacer) could improve the PEFR among the patients. IRCT2013091514666N1.

  9. The Effect of Training Inhalation Technique with or without Spacer on Maximum Expiratory Flow Rate and Inhaler Usage Skills in Asthmatic Patients: A Randomized Controlled Trial

    PubMed Central

    Rahmati, Hashem; Ansarfard, Fatemeh; Ghodsbin, Fariba; Ghayumi, Mohammad Ali; Sayadi, Mehrab

    2014-01-01

    Background: The most common treatment for asthma is transferring the drug into the lungs by inhaler devices. Besides, correct use of inhaled medication is required for effectiveness of pharmacotherapy. Thus, it is necessary to train the patients how to use Metered Dose Inhaler (MDI). This study aimed to determine the effect of training about MDI usage with or without spacer on maximum expiratory flow rate and inhaler usage skills in asthmatic patients. Methods: This randomized clinical trial was conducted on 90 asthmatic patients who were randomly divided into inhalation technique group with spacer, inhalation technique group without spacer, and a control group. Then, the Peak Expiratory Flow Rate (PEFR) was measured using a peak flow meter, as a basic test. In addition, the patients’ functional skills of inhalation technique were assessed using two checklists. Afterwards, 3 sessions of training were arranged for both groups. PEFR and the ability to use the MDI were evaluated immediately and 1 month after the intervention. Finally, the data were entered into the SPSS statistical software (v. 18) and analyzed using independent t-test and repeated measures ANOVA. Results: After the intervention, MDI usage skills improved in the two intervention groups compared to the control group (P<0.001). In addition, a significant difference was found between the intervention groups and the control group regarding the mean of PEFR after the intervention (P<0.001). However, no significant difference was observed between the two intervention groups (P=0.556). Conclusion: According to the results, providing appropriate training for asthmatic patients increased MDI usage skills, and both methods of inhalation (with or without spacer) could improve the PEFR among the patients. Trial Registration Number: IRCT2013091514666N1 PMID:25349864

  10. 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...

  11. 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...

  12. Effects of direct spiking of silicone oil into a model pMDI formulation.

    PubMed

    Fallon, John K; Peyron, Isabelle D; Hickey, Anthony J

    2013-05-01

    Silicone oil is used as a valve lubricant in pressurized metered dose inhalers (pMDIs). Its possible impact on drug delivery, through such effects as particle aggregation, has recently been discussed. To examine the effects of a range of directly spiked silicone oil amounts on pMDI performance. pMDI canisters containing a corticosteroid medicinal compound, HFA134a and accurately measured amounts of silicone oil (0, 200, 400 and 550 µg) were prepared. Samples were characterized for actuation weight, aerodynamic size (by Andersen cascade impaction, ACI), charge (by electrical low-pressure impaction, ELPI) and product appearance by visual imaging. Actuation weights were unaffected by silicone oil. A small increase in aerodynamic size was observed in the presence of silicone oil as a shift from stage 5 to impactor throat. No significant change in medicinal compound recovery was seen (t-tests, p > 0.05). Fine particle fraction as a percentage of dose delivered (FPF) was unchanged, as was particle size distribution derived from charge measurements, with the addition of silicone oil (t-tests, p > 0.05). Canister opening did not indicate container interaction but that sedimentation occurred in the presence of silicone oil. Decanted suspensions containing silicone oil were more transparent. Possible interactions inside and outside the pMDI canister are described. As demonstrated previously with an alternative experimental design the study showed that silicone oil has little effect on product performance, when added to a model pMDI formulation at levels that could potentially be observed as a leachable from the metering valve.

  13. Drug form selection in albuterol-containing metered-dose inhaler formulations and its impact on chemical and physical stability.

    PubMed

    Tzou, T Z; Pachuta, R R; Coy, R B; Schultz, R K

    1997-12-01

    New albuterol-containing metered-dose inhaler (MDI) formulations were under development to replace chlorofluorocarbon (CFC) propellants with more environmentally friendly hydrofluoroalkane (HFA) propellants. To achieve good chemical and physical stability of MDI formulations with HFA propellants, different drug forms were evaluated in model formulations (drug, oleic acid, and one of the following: P12/P11, P12/ethanol, P12, P134a/ethanol, P134a). The effects of drug form (base versus sulfate), propellant type (P12 versus P134a), and cosolvent type (P11 or ethanol versus none) on the chemical and physical stability were examined. The chemical stability of the formulations was determined by monitoring the percent drug remaining in the formulations using HPLC. The physical stability of the formulations was followed by visually assessing the suspension appearance, and by determining the mass median diameter (MMD) of the suspended particles using laser diffraction analysis. The drug form has a great impact on the chemical and physical stability of the formulations. The sulfate formulations were chemically stable up to 12 months when stored at 30 degrees C and 40 degrees C/85% relative humidity (RH). Poor chemical stability was observed for the base formulations, except for ethanol-free formulations (P12/P11, P12, and P134a) at 30 degrees C and a P134a formulation at 40 degrees C/85% RH. The chemical instability of albuterol base formulations at 30 degrees C correlates with its solubility. The presence of a cosolvent greatly improved the dispersion characteristics of both sulfate and base formulations. The sulfate formulations in the presence of a cosolvent (P12/P11, P12/ethanol, and P134a/ethanol) showed good physical stability when stored for up to 12 months at 30 degrees C and 40 degrees C/85% RH. The physical stability of the base formulations was not acceptable due to crystal growth/agglomeration in all formulations, except for the P12/P11 formulation. The physical

  14. Alcohol-based pressurised metered-dose inhalers for use in asthma: a descriptive study.

    PubMed

    Alrasbi, Maryam; Sheikh, Aziz

    2008-06-01

    Chlorofluorocarbons (CFCs) have historically served as the propellants of choice in pressurised metered-dose asthma inhalers, but concern has been raised in recent decades regarding their damaging effect on the ozone layer. Among the alternative propellants being considered is alcohol, which can be used as a co-solvent in asthma inhalers. Healthcare professionals need to be aware of alcohol-containing inhalers, since certain populations may have religious and/or cultural concerns regarding the use of such preparations. To identify pressurised metered-dose asthma inhalers which contain alcohol-based propellants. We searched the British National Formulary to identify companies that manufacture asthma treatments and wrote to them to enquire about which of their products contained alcohol and if so in what percentage. These direct contacts were supplemented by searching medical databases and the Internet for additional information. We identified 11 manufacturers of asthma inhalers, seven of which produced pressurised metered-dose inhalers; of these, six were willing to disclose the requested information, and information on the seventh product was obtained from an alternative valid source of information. Most CFC preparations contain alcohol, but CFC- and alcohol-free preparations do exist. Clinicians need to be aware that the majority of CFC-free inhalers contain alcohol. Alcohol-free, and CFC- and alcohol-free, preparations are available for the delivery of both rescue and preventative treatment and these should be considered for use in those patients who may have concern about alcohol-based treatments.

  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. The response of two different dosages of beclometasone dipropionate suspension for nebulization versus a standard dose of beclometasone dipropionate via a metered-dose inhaler on bronchoprovocation testing in adults with asthma.

    PubMed

    Bousquet, J; Meziane, H; Chanez, P; Mueser, M; Umile, A

    2003-02-01

    The objective of this double-blind, randomized, placebo-controlled, parallel-group study was to compare the pharmacodynamic effects and safety of beclometasone dipropionate (BDP) given by nebulization or metered-dose inhalation in adult patients with asthma. Following a 1-week run-in period, 40 patients, aged 18-60 years, with intermittent bronchial asthma were randomized to one of four treatment groups for 3 weeks (n = 10 in each group): beclometasone dipropionate (BDP) suspension for nebulization 1,600 microg day(-1) b.i.d. via a nebulizer, BDP suspension for nebulization 3,200 microg day(-1) b.i.d. via a nebulizer, BDP 800 microg day(-1) b.i.d. via a metered-dose inhaler (MDI) plus spacer, or placebo. At study end, comparable effects were reported for all active treatment groups on the primary pharmacodynamic endpoint of FEV1 in response to methacholine bronchial provocation testing, with a statistically significant improvement shown in the BDP 3,200 microg day(-1) suspension for nebulization group compared with pre-treatment for other parameters, including FEV1 and peak expiratory flow rates. All treatments were comparable. All treatments were equally well tolerated. No significant effects on cortisol levels were reported in any of the treatment groups.

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

    PubMed

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

    2005-01-01

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

  19. Inhalants

    MedlinePlus

    ... lack of coordination, euphoria (a feeling of intense happiness), and dizziness. Some users also experience lightheadedness, hallucinations ( ... on the type of inhalant used, the harmful health effects will differ. The table below lists some ...

  20. 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 ...

  1. Natural radionuclides in cigarette tobacco from Serbian market and effective dose estimate from smoke inhalation.

    PubMed

    Janković Mandić, Ljiljana; Đolić, Maja; Marković, Dragana; Todorović, Dragana; Onjia, Antonije; Dragović, Snežana

    2016-01-01

    The activity concentrations of natural radionuclides ((40)K, (210)Pb, (210)Po, (226)Ra and (228)Ra) in 17 most frequently used cigarette brands in Serbia and corresponding effective doses due to smoke inhalation are presented. The mean annual effective doses for (210)Pb and (210)Po were estimated to be 47.3 and 724 µSv y(-1) for (210)Pb and (210)Po, respectively. Serbia currently has the highest smoking rate in the world. The results of this study indicate the high contribution of the annual effective dose due to smoke inhalation to the total inhalation dose from natural radionuclides. The more effective implementation of actions for reducing smoking prevalence in Serbia is highly needed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. [A multi-center, randomized, double-blind, positive controlled clinical trial of salbutamol sulfate MDI without CFC in the treatment of asthma].

    PubMed

    2014-03-01

    To evaluate the efficacy and safety of domestically produced Salbutamol Sulfate metered dose inhaler (MDI) without chloro-fluro-carbon (CFC) in the treatment of asthmatic patients. A muticenter, randomized, double-blind, positive controlled clinical trial was conducted in asthmatic patients. The participants were randomized divided into trial group treated with domestically produced Salbutamol Sulfate Aerosol MDI (200 microg single-dose) and control group treated with imported Salbutamol Sulfate Aerosol MDI (200 microg single-dose). The lung function was measured by spirometry and a scoring questionaire before medications and 15, 30, 120 and 240 min post medications. A total of 238 patients were enrolled in the trial. Compared with baselines, the forced expiratory volume in 1 s (FEV1) of the participants in both groups increased significantly 15, 30, 120 and 240 min after medications (P < 0.05). There was no significant difference in the changes of FEV1 between the two groups (P > 0.05). Similarly, the forced vital capacity (FVC) and asthma symptomatic scores of the participants in both groups improved significantly after administration of medications (P < 0.05). There was no significant difference in the ratio of adverse reactions between the two groups (P > 0.05). In both groups, drugs were well tolerated. The domestically produced Salbutamol Sulfate Aerosol MDI without CFC is effective and safe for treating asthma.

  3. Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures.

    PubMed

    Gutting, Bradford W; Rukhin, Andrey; Marchette, David; Mackie, Ryan S; Thran, Brandolyn

    2016-11-01

    There is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous-Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose-response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively.

  4. Use of Respimat® Soft Mist™ Inhaler in COPD patients

    PubMed Central

    Anderson, Paula

    2006-01-01

    Events of the past decade have stimulated development of new drug formulations and delivery devices that have improved the efficiency, ease of use, and environmental impact of inhaled drug therapy. Respimat® Soft Mist™ Inhaler is a novel, multidose, propellant-free, hand-held, liquid inhaler that represents a new category of inhaler devices. The aerosol cloud generated by Respimat contains a higher fraction of fine particles than most pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs), and the aerosol spray exits the inhaler more slowly and for a longer duration than with pMDIs. This translates into higher lung drug deposition and lower oropharyngeal deposition, making it possible to give lower nominal doses of delivered drugs without lowering efficacy. In clinical trials in patients with COPD, bronchodilator drugs delivered from Respimat were equally effective at half of the dose delivered from a pMDI. In one study of inhaler preference, Respimat was preferred over the pMDI by patients with COPD and other obstructive lung diseases. Respimat is a valuable addition to the range of inhaler devices available to the patient with COPD. PMID:18046862

  5. Interference of chlorofluorocarbon (CFC)-containing inhalers with measurements of volatile compounds using selected ion flow tube mass spectrometry.

    PubMed

    Epton, Michael J; Ledingham, Katherine; Dummer, Jack; Hu, Wan-Ping; Rhodes, Bronwen; Senthilmohan, Senti T; Scotter, Jennifer M; Allardyce, Randall; Cook, Julie; Swanney, Maureen P

    2009-02-01

    Selected ion flow tube mass spectrometry (SIFT-MS) is a sensitive technique capable of measuring volatile compounds (VCs) in complex gas mixtures in real time; it is now being applied to breath analysis. We investigated the effect of inhalers containing chlorofluorocarbons (CFCs) on the detection and measurement of haloamines in human breath. SIFT-MS mass scans (MS) and selected ion monitoring (SIM) scans were performed on three healthy non-smoking volunteers before and after inhalation of the following medications: Combiventtrade mark metered-dose inhaler (MDI) (CFC-containing); Ventolintrade mark MDI (CFC-free); Atroventtrade mark MDI (CFC-free), Beclazonetrade mark MDI (CFC-containing); Duolintrade mark nebuliser. In addition, the duration of the persistence of the mass/charge ratios was measured for 20 h. Inhalers containing CFCs generated large peaks at m/z 85, 87, 101, 103 and 105 in vitro and in vivo, consistent with the predicted product ions of CFCs 12, 114 and 11. No such peaks were seen with Duolintrade mark via nebuliser, or CFC-free MDIs. We conclude that measurement of VCs, such as haloamines, with product ions of similar m/z values to the ions found for CFCs would be significantly affected by the presence of CFCs in inhalers. This issue needs to be accounted for prior to the measurement of VCs in breath in people using inhalers containing CFCs. Copyright 2009 John Wiley & Sons, Ltd.

  6. 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.

  7. The toxicity of continuous long-term low-dose formaldehyde inhalation in mice.

    PubMed

    Cheng, Jiaying; Zhang, Long; Tang, Yufu; Li, Zhenhai

    2016-12-01

    Although the toxicity of high-dose formaldehyde (FA) inhalation has been extensively analyzed in animals, the effect of continuous long-term exposure to low-dose FA has not been well documented. This study aims to evaluate the toxicity of continuous long-term low-dose FA inhalation in mice. Forty-eight Kunming male mice were equally randomized to three groups according to the dose of FA inhalation exposure: a control (0 mg/m(3)) group, a low-dose (0.08 mg/m(3)) group and a high-dose (0.8 mg/m(3)) group. The mice have been selected to expose to FA for different consecutive days at 24 h/day. The learning and memory functions, pathological changes in the lung and liver, and the percentage of CD4 (+) T and CD8 (+) T cells were observed and analyzed. It was found that continuous long-term inhalation of FA at relatively low doses could impair the learning and memory functions and induce pathological changes in the lung and liver, but did not seem to significantly affect the number of immune (CD4 (+) T and CD8 (+) T) cells.

  8. Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

    PubMed

    Visser, R; Kelderman, S; de Jongh, F H C; van der Palen, J; Thio, B J

    2015-10-01

    Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 μg or 400 μg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 μg salbutamol compared to 200 μg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 μg compared to 200 μg salbutamol with a BAI does improve reversibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

    Boss, H; Minic, P; Nave, R

    2010-01-01

    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). To compare the pharmacokinetic (PK) parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus(™)). 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. 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. 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.

  10. 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

  11. 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

  12. Deposition of inhaled nanoparticles in the rat nasal passages: dose to the olfactory region.

    PubMed

    Garcia, Guilherme J M; Kimbell, Julia S

    2009-12-01

    In vivo experiments have shown that nanoparticles depositing in the rat olfactory region can translocate to the brain via the olfactory nerve. Quantitative predictions of the dose delivered by inhalation to the olfactory region are needed to clarify this route of exposure and to evaluate the dose-response effects of exposure to toxic nanoparticles. Previous in vivo and in vitro studies quantified the percentage of inhaled nanoparticles that deposit in the rat nasal passages, but olfactory dose was not determined. The dose to specific nasal epithelium types is expected to vary with inhalation rate and particle size. The purpose of this investigation, therefore, was to develop estimates of nanoparticle deposition in the nasal and, more specifically, olfactory regions of the rat. A three-dimensional, anatomically accurate, computational fluid dynamics (CFD) model of the rat nasal passages was employed to simulate inhaled airflow and to calculate nasal deposition efficiency. Particle sizes from 1 to 100 nm and airflow rates of 288, 432, and 576 ml/min (1, 1.5, and 2 times the estimated resting minute volume) were simulated. The simulations predicted that olfactory deposition is maximum at 6-9% of inhaled material for 3- to 4-nm particles. The spatial distribution of deposited particles was predicted to change significantly with particle size, with 3-nm particles depositing mostly in the anterior nose, while 30-nm particles were more uniformly distributed throughout the nasal passages.

  13. A pilot study comparing the antispasmodic effects of inhaled salmeterol, salbutamol and ipratropium bromide using different aerosol devices on muscarinic bronchoconstriction in healthy cats.

    PubMed

    Leemans, Jérôme; Kirschvink, Nathalie; Bernaerts, Frédérique; Clercx, Cécile; Cambier, Carole; Gustin, Pascal

    2009-05-01

    This study compared the duration and magnitude of the antispasmodic effects of salmeterol (SLM), salbutamol (SAL), ipratropium bromide (IB) and the combination of SAL and IB (SAL/IB) against carbachol-induced bronchoconstriction in healthy cats, and investigated the gain in efficacy using a two or fourfold increase in drug dosages. The drug regimens used were: (1) SLM 25 microg, SAL 100 microg, IB 20 microg and SAL/IB 100 microg/20 microg for bronchodilators delivered by a metered-dose inhaler (MDI); (2) SAL 3.75 mg and IB 62.5 microg for nebulised (NEB) medications. To monitor the bronchodilator effect, airway responsiveness was assessed at different time points using barometric whole-body plethysmography and calculation of the concentration of inhaled carbachol inducing a 300% increase of baseline Penh (enhanced pause), an estimator of airflow limitation. Maximum C-Penh300 was recorded 15 min after NEB SAL, IB MDI, NEB IB and 1h after SAL MDI and 4h after SLM MDI, respectively. C-Penh300 was significantly different from control values (without treatment) up to 24h for SLM MDI, 8h for IB MDI and 4h for other drugs. In terms of efficacy, SAL/IB MDI showed a synergistic antispasmodic effect at 15 min, 4h and 8h after administration. A fourfold increase of the initial dose of IB MDI and NEB IB significantly increased C-Penh300. Despite a fourfold dose increase, SLM displayed the weakest degree of bronchoprotection compared to other bronchodilators. The study provides evidence that inhaled bronchodilators are efficient at preventing muscarinic-induced bronchospasm in healthy cats and that SAL and IB appear to be short-acting bronchodilators in contrast to SLM.

  14. Acute, Low-dose CO Inhalation does not Alter Energy Expenditure during Submaximal Exercise.

    PubMed

    Kane, L A; Ryan, B J; Schmidt, W; Byrnes, W C

    2016-01-01

    Carbon monoxide, a gas known most widely for its toxic effects at high doses, is receiving increased attention for its role as a physiological signaling molecule and potential therapeutic agent when administered in low doses. We sought to quantify any changes to oxygen consumption and energy expenditure during submaximal exercise after low-dose CO inhalation. 9 active individuals completed 4 graded submaximal exercise tests, with each test occurring during a separate visit. For their first exercise test, subjects inhaled CO or room air (1.2 mL·kg(-1) body mass) in a randomized, subject-blind fashion. A second test was repeated 24 h later when the inhaled gas should have cleared the system. Subjects repeated study procedures with the alternate dose after a washout period of at least 2 days. Low-dose CO administration did not affect oxygen consumption or energy expenditure during submaximal exercise immediately or 24 h following its administration. Increases in heart rate, blood [lactate], and perceived exertion were observed following acute CO inhalation but these effects were absent after 24 h. The results of this study suggest that low-dose CO administration does not influence the energetics of submaximal exercise, but it acutely increases the relative intensity associated with absolute workloads below the lactate threshold. © Georg Thieme Verlag KG Stuttgart · New York.

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

    PubMed Central

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

    2017-01-01

    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

  16. 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.

  17. 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

  18. 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...

  19. 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...

  20. A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices.

    PubMed

    van der Palen, Job; Thomas, Mike; Chrystyn, Henry; Sharma, Raj K; van der Valk, Paul Dlpm; Goosens, Martijn; Wilkinson, Tom; Stonham, Carol; Chauhan, Anoop J; Imber, Varsha; Zhu, Chang-Qing; Svedsater, Henrik; Barnes, Neil C

    2016-11-24

    Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57-70%) made no errors using ELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other devices (all P⩽0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers.

  1. A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices

    PubMed Central

    van der Palen, Job; Thomas, Mike; Chrystyn, Henry; Sharma, Raj K; van der Valk, Paul DLPM; Goosens, Martijn; Wilkinson, Tom; Stonham, Carol; Chauhan, Anoop J; Imber, Varsha; Zhu, Chang-Qing; Svedsater, Henrik; Barnes, Neil C

    2016-01-01

    Errors in the use of different inhalers were investigated in patients naive to the devices under investigation in a multicentre, single-visit, randomised, open-label, cross-over study. Patients with chronic obstructive pulmonary disease (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the patient information leaflet (PIL). A trained investigator assessed critical errors (i.e., those likely to result in the inhalation of significantly reduced, minimal or no medication). If the patient made errors, the investigator demonstrated the correct use of the inhaler, and the patient demonstrated inhaler use again. Fewer COPD patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%); Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%); Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57–70%) made no errors using ELLIPTA and did not require investigator instruction. Instruction was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs 8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60 (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other devices (all P⩽0.002). Significantly, fewer COPD patients using ELLIPTA made critical errors after reading the PIL vs other inhalers. More asthma and COPD patients preferred ELLIPTA over comparator inhalers. PMID:27883002

  2. Inhalation threshold of toxicological concern (TTC) - Structural alerts discriminate high from low repeated-dose inhalation toxicity.

    PubMed

    Schüürmann, Gerrit; Ebert, Ralf-Uwe; Tluczkiewicz, Inga; Escher, Sylvia E; Kühne, Ralph

    2016-03-01

    The threshold of toxicological concern (TTC) of a compound represents an exposure value below which the associated human health risk is considered negligible. As such, this approach offers assessing the risk of potential toxicants when little or no toxicological information is available. For the inhalation repeated-dose TTC, the goal was to derive structural alerts that discriminate between high- and low-toxic compounds. A further aim was to identify physicochemical parameters related to the inhalation-specific bioavailability of the compounds, and to explore their use as predictors of high vs low toxicity. 296 compounds with subacute, subchronic and chronic inhalation toxicity NOEC (no-observed effect concentration) values were subdivided into three almost equal-sized high-, medium- and low-toxic (HTox, MTox, LTox) potency classes. Whereas the derived 14 HTox and 7 LTox structural alerts yield an only moderate discrimination between these three groups, the high-toxic vs low-toxic mis-classification is very low: LTox-predicted compounds are not HTox to 97.5%, and HTox-predicted compounds not LTox to 88.6%. The probability of a compound being HTox vs LTox is triggered further by physicochemical properties encoding the tendency to evaporate from blood. The new structural alerts may aid in the predictive inhalation toxicity assessment of compounds as well as in designing low-toxicity chemicals, and provide a rationale for the chemistry underlying the toxicological outcome that can also be used for scoping targeted experimental studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Speed of onset of bronchodilator response to salbutamol inhaled via different devices in asthmatics: a bioassay based on functional antagonism

    PubMed Central

    Lavorini, Federico; Geri, Pietro; Mariani, Laura; Marmai, Cecilia; Maluccio, Nazzarena Maria; Pistolesi, Massimo; Fontana, Giovanni A

    2006-01-01

    Aims To evaluate the speed of onset of bronchodilation following salbutamol administered via a metered-dose inhaler with a spacer (pMDI + Volumatic) and a dry-powder inhaler (Diskus), as well as the relative potencies of these devices in asthmatic patients with methacholine-induced bronchoconstriction. Methods Eighteen patients inhaled methacholine (MCh) until FEV1 decreased by 35% of control. Following administration of placebo, 200 µg salbutamol or 400 µg salbutamol through the pMDI + Volumatic or the Diskus, we calculated the time elapsed from drug administration and the appearance of a 90% increase in post-MCh forced vital capacity (FVC), FEV1 and volume-adjusted mid-expiratory flow (recovery times). The salbutamol doses to be delivered by the two inhalation devices to achieve similar recovery times and the relative potencies of the devices were calculated by using the 2-by-2 Finney parallel regression method. Results For all functional variables, recovery times were significantly (P < 0.01) shorter in pMDI + Volumatic than Diskus trials. The salbutamol doses to be delivered by the Diskus to achieve recovery times for FVC, FEV1 and volume-adjusted mid-expiratory flow similar to those obtained with 200 µg salbutamol administered via the pMDI + Volumatic were 558 (95% CI 537, 579) µg, 395 (95% CI 388, 404) µg and 404 (95% CI 393, 415) µg, respectively, and corresponded to relative potencies of 2.79 (95% CI 2.68, 2.90), 1.98 (95% CI 1.94, 2.02), and 2.02 (95% CI 1.96, 2.07). Conclusions Administration of salbutamol via the pMDI + Volumatic provides faster reversal of induced bronchoconstriction than via the Diskus. The salbutamol dose targeting the lungs with the pMDI + Volumatic is approximately twice that with the Diskus. PMID:16995861

  4. Asthma management and inhalation techniques among community pharmacists in 2009: a comparison with the 1999 survey.

    PubMed

    Casset, Anne; Meunier-Spitz, Marion; Rebotier, Pauline; Lefèvre, Hassina; Barth, Christian; Heitz, Christiane; de Blay, Frédéric

    2014-11-01

    In a 1999 survey, community pharmacists from the Alsace region of France had a reasonably good knowledge of asthma treatment and prevention, but their skill in the use of asthma inhalation devices left room for improvement. Since then, health authorities have encouraged the involvement of community pharmacists in patient care and education in order to improve asthma control. The aim of this study was to assess the change in the knowledge of asthma management and inhaler technique skills of community pharmacists in the same geographic area after a 10-year interval. In 2009, 86 randomly selected community pharmacists from the Alsace region answered a standardized questionnaire about their theoretical knowledge of and practical attitude toward asthma management and inhaled delivery systems, following which their skills in the use of four inhalation devices (pressurized metered-dose inhaler (pMDI) with/without a spacer, breath-actuated pMDI and dry powder inhaler (DPI)) were evaluated. Very few pharmacists were required to manage an acute asthma exacerbation at the pharmacy, but all responded well by administering a short-acting inhaled β2-agonist. Theoretical knowledge of asthma management (criteria of severity of asthma exacerbation, guidelines and drugs triggering asthma exacerbations) was still average. Compared with 1999, they were twice as confident in demonstrating inhaler use, and their skills in using the pMDI, breath-actuated pMDI and DPI had improved significantly (p < 0.001). Since 1999, pharmacists' skill in the use of inhalers has improved, but theoretical knowledge of asthma management is still average, pointing to the importance of continuing pharmaceutical education.

  5. Performance of pressurized metered-dose inhalers at extreme temperature conditions.

    PubMed

    Morin, Chelsea M D; Ivey, James W; Titosky, Jordan T F; Suderman, Jonathan D; Olfert, Jason S; Vehring, Reinhard; Finlay, Warren H

    2014-11-01

    The performance of pressurized metered-dose inhalers (pMDIs) under a variety of temperature conditions was investigated. The effects of both inhaler temperature and ambient temperature were considered. The inhaler temperature ranged from -13.0°C to 41.7°C and the ambient temperature ranged from -12.0°C to 41.7°C. The in vitro lung dose was measured for four widely available pMDIs: Airomir(TM) , QVAR(TM) , Symbicort(®) , and Ventolin(®) . The in vitro lung dose through an Alberta Idealized Throat was measured by gravimetric assay, which was verified by UV spectroscopic assay. A decrease in the in vitro lung dose was observed for all evaluated pMDIs when ambient temperature and device temperature were simultaneously reduced, decreasing on average by 70% at the coldest temperatures, whereas increasing on average by 25% at the elevated temperature condition. In vitro lung dose is strongly dependent on both inhaler temperature and ambient temperature with the tested pMDIs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. Development of a dry powder inhaler, the Ultrahaler, containing triamcinolone acetonide using in vitro-in vivo relationships.

    PubMed

    Lim, Joe G P; Shah, Bharti; Rohatagi, Shashank; Bell, Alex

    2006-01-01

    Triamcinolone acetonide (TAA) is safe and effective corticosteroid that is marketed as an MDI (metered dose inhaler) (Azmacort) for the treatment of asthma. A novel dry powder inhaler (DPI), the Ultrahaler, has been developed to deliver Azmacort as another alternative to provide non-CFC formulation for the asthmatic patients. The Ultrahaler is breath actuated and, unlike MDI, does not require coordination of inhalation with the actuation of the device. However, with the Ultrahaler device, like any dry powder inhalation device, the challenge was the on-target and uniform delivery of the drug at the site of action (lungs) with different dose strengths. Due to the complexities of oral inhaled formulations and the topical nature of drug delivery to the lung for efficacy, the reformulation requires careful consideration and support throughout their development, using a combination of in vitro and in vivo studies. This paper describes in vitro studies and two clinical pharmacokinetic studies conducted in a sequence that helped to establish optimum doses for the Ultrahaler. In vitro data were used to guide the initial selection of doses that were then compared in vivo using a pharmacokinetic study with a charcoal block. The in vitro tests included quantifying the target-delivered dose, dose uniformity throughout the life of the device, and the particle size distribution. Particle size distribution was measured using multistage liquid impinger (MSLI) or the Andersen Cascade Impactor (ACI). For in vitro testing, TAA was measured by HPLC methods. Based on the preliminary in vitro data for the respirable fraction, dose strengths with an MDI and the Ultrahaler for the first study were determined. The in vivo assessment consisted of a four-way crossover study following oral inhalation using both MDI (75 and 225 microg/actuation, reference treatment) and comparable respirable doses in the DPI (130 and 360 microg/actuation) devices in healthy volunteers in the presence (lung

  7. In vitro dose comparison of Respimat(®) inhaler with dry powder inhalers for COPD maintenance therapy.

    PubMed

    Ciciliani, Anna-Maria; Langguth, Peter; Wachtel, Herbert

    2017-01-01

    Combining in vitro mouth-throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD) simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD) treatment. The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL) was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI). Idealized breathing patterns from COPD patient groups - moderate and very severe COPD - were applied. Theoretical lung deposition patterns were assessed by an individual path model. For the Respimat the mDTL was found to be 59% (SD 5%) for the moderate COPD breathing pattern and 67% (SD 5%) for very severe COPD breathing pattern. The percentages refer to nominal dose (ND) in vitro. This is in the range of 44%-63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2%) for moderate disease simulation and 51% (SD 2%) for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2%) for moderate and 42% (SD 1%) for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3%) for moderate and 55% (SD 2%) for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3%) and 41% (SD 2%), respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that deposition occurs mainly in the small airways. In summary, Respimat showed the lowest amount of particles depositing in the mouth-throat model and the highest amount reaching all regions of the simulation lung model.

  8. In vitro dose comparison of Respimat® inhaler with dry powder inhalers for COPD maintenance therapy

    PubMed Central

    Ciciliani, Anna-Maria; Langguth, Peter; Wachtel, Herbert

    2017-01-01

    Background Combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD) simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD) treatment. Methods The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL) was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI). Idealized breathing patterns from COPD patient groups – moderate and very severe COPD – were applied. Theoretical lung deposition patterns were assessed by an individual path model. Results and conclusion For the Respimat the mDTL was found to be 59% (SD 5%) for the moderate COPD breathing pattern and 67% (SD 5%) for very severe COPD breathing pattern. The percentages refer to nominal dose (ND) in vitro. This is in the range of 44%–63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2%) for moderate disease simulation and 51% (SD 2%) for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2%) for moderate and 42% (SD 1%) for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3%) for moderate and 55% (SD 2%) for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3%) and 41% (SD 2%), respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that deposition occurs mainly in the small airways. In summary, Respimat showed the lowest amount of particles depositing in the mouth–throat model and the highest amount reaching all regions of the simulation lung model. PMID:28603412

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

    PubMed

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

    1997-07-01

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

  10. High-Dose Inhaled Salbutamol Does Not Improve 10-km Cycling Time Trial Performance.

    PubMed

    Koch, Sarah; Ahn, Joeungyoen Rei; Koehle, Michael Stephen

    2015-11-01

    β2-agonists are on the World Anti-Doping Agency's list of prohibited substances; however, athletes are allowed to treat symptoms of exercise-induced bronchoconstriction with a maximal daily dose of 1600 μg of salbutamol when taken by inhalation. This study aimed to investigate whether 1600 μg of salbutamol leads to enhanced time trial performance in trained, competitive male cyclists with and without exercise-induced bronchoconstriction on the basis of inhaled dose per kilogram of body weight. In a randomized crossover design, 20 trained male cyclists (eight with positive eucapnic voluntary hyperpnea challenge (EVH+) and 12 with negative EVH challenge (EVH-) performed two simulated 10-km time trials on a cycle ergometer 30 min after the inhalation of either 1600 μg of salbutamol or placebo. Lung function, assessed by forced expiratory volume in 1 s (FEV1), was measured immediately before and 15 min after inhalation. The main performance outcome was mean power output. After the inhalation of salbutamol, FEV1 was significantly increased by 6.4% (4.9%) versus 1.0% (4.4%) with placebo (P < 0.001). Despite this increase in FEV1, mean power output during the salbutamol time trial was not increased regardless of relative dose per kilogram of body weight and asthma status. Mean heart rate (P = 0.01), respiratory rate (P = 0.01), minute ventilation (P = 0.03) and perceived leg discomfort (P = 0.03) were significantly increased in the salbutamol condition. The inhalation of 1600 μg salbutamol improved FEV1 regardless of EVH status but did not improve 10-km time trial performance in trained competitive male cyclists regardless of relative dose per kilogram of body weight or EVH status. Significant increases in heart rate and minute ventilation occurred secondary to stimulation of the adrenergic nervous system.

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

    PubMed Central

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

    2012-01-01

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

  12. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    EPA Science Inventory

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

  13. 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...

  14. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    EPA Science Inventory

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

  15. 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...

  16. Inhaled low-dose iloprost for pulmonary hypertension: a prospective, multicenter, open-label study.

    PubMed

    Sun, Yun-Juan; Xiong, Chang-Ming; Shan, Guang-Liang; Gu, Qing; Zeng, Wei-Jie; Lu, Xian-Ling; Zhu, Feng; Liu, Zhi-Hong; Ni, Xin-Hai; He, Jian-Guo

    2012-06-01

    Inhaled iloprost (average >30 µg/d) has been considered an effective treatment for severe pulmonary hypertension (PH). Further evidence also showed that low-dose iloprost given intravenously was equally effective as high-dose iloprost in the therapy of systemic sclerosis. Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost. Sixty-two patients with PH were enrolled and initiated with neubulizedlow-dose iloprost (2.5 µg per inhalation, 6× daily) for 24 weeks in 13 medical centers in China. Efficacy endpoints included changes in 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), and hemodynamic parameters. Fourteen patients (22.6%) prematurely discontinued the study: 8 due to clinical worsening (6 in WHO-FCIII-IV at baseline), 4 because of protocol change, and 2 patients lost during follow-up. In the remaining 48 patients, 6MWD was increased from 356 ± 98 meters to 414 ± 99 meters (P < 0.001) and WHO-FC improved significantly (P = 0.006) after 24-week inhalation therapy. Cardiac output, cardiac index, and mixed venous oxygen saturation improved significantly compared with baseline (n = 34, P < 0.05). Most of the hemodynamic parameters improved significantly in patients in WHO-FC II (P < 0.05) but not in patients in WHO-FCIII-IV. Low-dose iloprost inhalation significantly improved exercise capacity and functional status in patients with PH. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FCI-II but not in patients with WHO-FCIII-IV, suggesting the importance of early treatment in patients with advanced disease stages. © 2012 Wiley Periodicals, Inc.

  17. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Assessment of skills using a spacer device for a metered-dose inhaler and related independent predictive factors in caregivers of asthmatic preschool children.

    PubMed

    Topal, Erdem; Celiksoy, Mehmet Halil; Catal, Ferhat; Sinanoglu, Muhammed S; Karakoc, Habib Tadayyon Einaddin; Sancak, Recep; Ozturk, Fadıl

    2016-02-01

    The correct use of inhalation devices is essential for successful therapy. We aimed to evaluate the skills in the use of a spacer device with an metered-dose inhaler (MDI) and factors that influence this skill in asthmatic preschool children's caregivers. The caregivers of 12-month-old to 72-month-old children were interviewed face-to-face and filled out questionnaires. To assess use of the spacer device, we asked the caregivers to verbally describe and demonstrate how they used the device. A total of 244 patients were included in the study, and 142 (58.2%) of the caregivers demonstrated every step for using the spacer device. The most frequently mistaken step was waiting for 30 seconds for the second puff after the first puff. When statistically significant and clinically important parameters were analyzed in a logistic regression model, the parameters satisfaction with the spacer device (odds ratio [OR] 29.9; 95% confidence interval [CI], 7.64 to 117.39; p < 0.001), a university graduate (OR 13.5; 95% CI, 3.36 to 54.8; p < 0.001), family monthly income of more than US$1500 (OR 5.3; 95% CI, 2.16 to 13.39; p < 0.001), device training provided by a clinical trainer (OR 12.3; 95% CI, 4.82 to 31.73; p < 0.001), regular follow-ups (OR 3.6; 95% CI, 1.57 to 8.47; p = 0.003), and the absence of a severe attack during the last year (OR 6.5; 95% CI, 2.64 to 16.43; p < 0.001) were found to be independent factors that affected the correct demonstration of the device. The factors most effective in the correct use of the MDI spacer device were satisfaction with the device, training having been given by a clinical trainer on this subject, and the caregiver being a university graduate. © 2015 ARS-AAOA, LLC.

  19. 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.

  20. 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....

  1. 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....

  2. 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

  3. Cycling to work in London and inhaled dose of black carbon.

    PubMed

    Nwokoro, Chinedu; Ewin, Clare; Harrison, Clare; Ibrahim, Mubin; Dundas, Isobel; Dickson, Iain; Mushtaq, Naseem; Grigg, Jonathan

    2012-11-01

    Modelling studies suggest that urban cycling is associated with an increased inhaled dose of fossil fuel-derived black carbon (BC). Using the amount of black material in airway macrophages as a marker of long-term inhaled BC, we sought to compare inhaled BC dose in London (UK) cyclists and non-cyclists. Airway macrophage carbon was assessed in 28 (58%) out of 48 healthy adults (14 cyclists and 14 non-cyclists) who attended for induced sputum. Short-term (24 h) exposure to BC was assessed on a representative working day in 27 out of 28 subjects. Serum interleukin (IL)-1β, IL-2, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor and tumour necrosis factor (TNF)-α were assessed in 26 out of the 28 subjects. Cyclists were found to have increased airway macrophage carbon when compared with non-cyclists (mean ± se 1.81 ± 0.21 versus 1.11 ± 0.07 μm(2); p<0.01). Short-term monitoring showed no difference in 24 h BC exposure between the two groups. However, cyclists were exposed to higher concentrations of BC during commuting (p<0.01). Airway macrophage carbon was associated with monitored commute BC (n=28; r=0.47, p<0.05). TNF-α was found to be increased in cyclists (p<0.05), but no other cytokines were increased. Commuting to work by bicycle in London is associated with increased long-term inhaled dose of BC. Whether cycling per se increases inhaled BC dose remains unclear.

  4. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals.

    PubMed

    Adkins, B; O'Connor, R W; Dement, J M

    1987-06-01

    Laboratory animals were exposed by inhalation for 2 hr/day (acute) or 6 hr/day (four consecutive days, repeated dose) to methyl isocyanate (MIC). Exposures were conducted in stainless steel and glass inhalation exposure chambers placed in stainless steel, wire mesh cages. MIC was delivered with nitrogen via stainless steel and Teflon supply lines. Chamber concentrations ranged from 0 to 60 ppm and were monitored continuously with infrared spectrophotometers to 1 ppm and at 2-hr intervals to 20 ppb with a high performance liquid chromatograph equipped with a fluorescence detector. Other operational parameters monitored on a continuous basis included chamber temperature (20-27 degrees C), relative humidity (31-64%), static (transmural) pressure (-0.3 in.), and flow (300-500 L/min). The computer-assistance system interfaced with the inhalation exposure laboratory is described in detail, including the analytical instrumentation calibration system used throughout this investigation.

  5. New isocyanate-specific albumin adducts of 4,4'-methylenediphenyl diisocyanate (MDI) in rats.

    PubMed

    Kumar, Anoop; Dongari, Nagaraju; Sabbioni, Gabriele

    2009-12-01

    4,4'-Methylenediphenyl diisocyanate (MDI) is the most important of the isocyanates used as intermediates in the chemical industry. Among the main types of damage after exposure to low levels of MDI are lung sensitization and asthma. Albumin adducts of MDI might be involved in the etiology of sensitization reactions. It is, therefore, necessary to have sensitive and specific methods for monitoring the isocyanate exposure of workers. To date, urinary metabolites or protein adducts have been used as biomarkers in workers exposed to MDI. However, with these methods it is not possible to determine whether the biomarkers result from exposure to MDI or to the parent aromatic amine 4,4'-methylenedianiline (MDA). This work presents a procedure for the determination of isocyanate-specific albumin adducts. In a long-term experiment, designed to determine the carcinogenic and toxic effects of MDI, rats were exposed chronically for 3 months, to 0.0 (control), 0.26, 0.70, and 2.06 mg MDI/m(3) as aerosols. Albumin was isolated from plasma, digested with Pronase E, and analyzed by LC-MS/MS. MDI formed adducts with lysine: N(6)-[({4-[4-aminobenzyl]phenyl}amino)carbonyl]lysine (MDI-Lys) and N(6)-[({4-[4-(acetylamino)benzyl]phenyl}amino)carbonyl] lysine (AcMDI-Lys). For the quantitation of the adducts in vivo, isotope dilution mass spectrometry was used to measure the adducts in 2 mg of albumin. The adducts found in vivo (MDI-Lys and AcMDI-Lys) and the corresponding isotope labeled compounds (MDI-[(13)C(6)(15)N(2)]Lys and Ac[(2)H(4)]MDI-Lys) were synthesized and used for quantitation. The MDI-Lys levels increased from 0-24.8 pmol/mg albumin, and the AcMDI-Lys levels increased from 0-1.85 pmol/mg albumin. The mean ratio of MDI-Lys/AcMDI-Lys for each dose level was greater than >20. The albumin adducts correlate with other biomarkers measured in the same rats in the past: urinary metabolites and hemoglobin adducts released after mild base hydrolysis. This method will enable one to

  6. A review of ipratropium bromide/fenoterol hydrobromide (Berodual) delivered via Respimat Soft Mist Inhaler in patients with asthma and chronic obstructive pulmonary disease.

    PubMed

    Kässner, Frank; Hodder, Rick; Bateman, Eric D

    2004-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) can be effectively treated by the use of bronchodilator therapies delivered by inhalation. Berodual is a fixed combination of the anticholinergic agent ipratropium bromide (IB) and the beta2-adrenergic agonist fenoterol hydrobromide (FEN). IB/FEN has been available for the treatment of asthma and COPD in a pressurised metered dose inhaler (MDI) [pMDI] formulation for many years. The pMDI is the most widely used device for the delivery of inhaled medications, such as IB/FEN. However, most conventional pMDIs contain chlorofluorocarbon (CFC) propellants, which are currently being withdrawn because of their detrimental effects on the environment. This has resulted in alternative methods of drug delivery being developed. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that generates a fine, slow-moving cloud (the Soft Mist) which can be easily inhaled. Scintigraphic studies have shown that this improves deposition of drugs in the lung and results in less oropharyngeal deposition than the CFC-MDI. A clinical development programme has been conducted to compare the efficacy and safety of IB/FEN delivered via Respimat SMI with that of IB/FEN via CFC-MDI in the treatment of patients with asthma or COPD. Five clinical studies (two phase II and three phase III) investigated dosages of IB/FEN 5/12.5 microg to 320/800 microg via Respimat SMI in single and multiple dose administration regimens. Four of the trials were conducted in patients with asthma (three in adults and one in children), while one phase III trial was conducted in patients with COPD. In phase III, 2058 patients participated, with a total of 1112 patients treated with IB/FEN via Respimat SMI. In the phase III studies, each dose from Respimat SMI was given in one actuation compared with two actuations with the CFC-MDI. In the paediatric asthma phase III study, all CFC-MDI doses were delivered via a spacer device. The results of

  7. Use of inhaler devices in pediatric asthma.

    PubMed

    De Benedictis, Fernando Maria; Selvaggio, David

    2003-01-01

    Inhalation is the preferred route for asthma therapy, since it offers a rapid onset of drug action, requires smaller doses, and reduces systemic effects compared with other routes of administration. Unfortunately, inhalation devices are frequently used in an empirical manner rather than on evidence-based awareness.A wide variety of nebulizers are available. Conventional jet nebulizers are highly inefficient, as much of the aerosol is wasted during exhalation. However, incorporating an extra open vent into the system has considerably increased the amount of drug that patients receive. Breath-assisted open vent nebulizers limit the loss of aerosol during exhalation, but are dependent on the patient's inspiratory flow. Ultrasonic nebulizers produce a high mass output and have a short nebulization time, but are inefficient for delivering suspensions or viscous solutions. Adaptive aerosol delivery devices release a precise dose that is tailored to the individual patient's breathing pattern. Nebulizers have several drawbacks, and their use should be limited to patients who cannot correctly manage other devices.Pressurized metered-dose inhalers (pMDI) are practical, cheap and multidose. However, there are several problems with their use. Breath-actuated MDI are easy to use and can be activated by very low flow. However, young children may not be able to use them efficiently. Dry powder inhalers (DPI) are portable and easy to use. They are indicated either for rescue bronchodilator therapy or for regular treatment with inhaled corticosteroids and long-acting bronchodilators. The use of spacers reduces oropharyngeal deposition and improves drug delivery to the lung. Spacers do not require patient coordination, but some general rules must be followed for their optimal use.Thus, the choice of a delivery device mainly depends on the age of the patient, the drug to be administered and the condition to be treated. Proper education is also essential when prescribing an inhalation

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

    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. 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). 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. 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 and FPD showed little flow dependency.

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

    Integrated Risk Information System (IRIS)

    TOXICOLOGICAL REVIEW of METHYLENE DIPHENYL DIISOCYANATE ( MDI ) ( CAS No . 101 - 68 - 8 and 9016 - 87 - 9 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) February 1998 U.S . ENVIRONMENTAL PROTECTION AGENCY WASHINGTON , DC TABLE OF CONTENTS TOXICOLOGICAL REVIEW

  11. Equivalence of two steroid-containing inhalers: easyhaler multidose powder inhaler compared with conventional aerosol with large-volume spacer.

    PubMed

    Koskela, T; Hedman, J; Ekroos, H; Kauppinen, R; Leinonen, M; Silvasti, M; Tukiainen, H

    2000-01-01

    An equivalence study was conducted in which the efficacy and safety of a daily dose of 800 microgram of beclomethasone diproprionate administered via a multidose powder inhaler, Easyhaler, and via a metered-dose inhaler (MDI) with a large-volume spacer were compared in adult, newly diagnosed, steroid-naive asthmatic patients. Acceptability of the medications was also compared. One hundred and forty-four patients were recruited into the double-blind, double-dummy, randomised, parallel-group multicentre study. The study treatment period was 8 weeks. It was preceded by a 2-week run-in period. Morning and evening peak expiratory flow (PEF), numbers of inhalations of a sympathomimetic and asthma symptoms were recorded daily. Spirometry and histamine challenge were performed, and health-related quality of life and morning serum cortisol levels measured during control visits. Criteria indicating treatment equivalence were met. The mean of the primary outcome variable, morning PEF, increased significantly, from 426 to 461 litres/min in the Easyhaler group and from 436 to 467 litres/min in the MDI+spacer group. Similar improvements between groups were also seen in relation to all secondary variables. Changes in serum cortisol levels were minor. In 6 out of 10 questions about device acceptability, the majority of patients rated Easyhaler as better than the MDI+spacer combination. It was concluded that the devices tested were equivalent in terms of efficacy and safety. Copyright 2000 S. Karger AG, Basel.

  12. 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.

  13. Comparison of patient-reported outcomes during treatment with adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler versus fixed-dose fluticasone propionate/salmeterol dry powder inhaler in patients with asthma.

    PubMed

    O'Connor, Richard D; Patrick, Donald L; Parasuraman, Bhash; Martin, Paula; Goldman, Mitchell

    2010-03-01

    Assessment of patient-reported outcomes is important in evaluating the impact of asthma treatment. This study was conducted to compare effects of adjustable- and fixed-dose budesonide/formoterol pressurized metered-dose inhaler with fixed-dose fluticasone propionate/salmeterol dry powder inhaler regimens on patient-reported outcomes in patients aged > or =18 years with moderate to severe asthma. In this phase III, randomized, open-label study, 1225 patients were randomized 2:1 to fixed-dose budesonide/formoterol 160/4.5 microg x 2 inhalations (320/9 mug) twice daily or fixed-dose fluticasone propionate/salmeterol 250/50 microg twice daily for 1 month. In the subsequent 6 months, patients receiving fixed-dose fluticasone propionate/salmeterol continued therapy, whereas those receiving fixed-dose budesonide/formoterol were randomized 1:1 to fixed-dose or adjustable-dose budesonide/formoterol (adjustable from 320/9 microg twice daily to 320/9 microg once daily or 640/18 microg twice daily). Mean improvements from baseline to end of treatment in the Asthma Quality of Life Questionnaire (standardized) overall and individual domain scores and the Asthma Control Questionnaire score were clinically important (> or =0.5 points) for all treatments. Patients in both budesonide/formoterol groups reported greater treatment satisfaction on the Asthma Treatment Satisfaction Measure questionnaire than patients in the fluticasone propionate/salmeterol dry powder inhaler group for the attributes of timely relief of symptoms (p < or = .037) and feel medication working (p < or = .020). Onset of Effect Questionnaire scores showed a greater percentage of patients perceiving onset of effect with budesonide/formoterol regimens versus fixed-dose fluticasone propionate/salmeterol (p < or = .002). Treatment regimens did not differ regarding improvements in asthma-specific quality of life and asthma control. Questions related to perceived rate of onset and feeling medication working in the

  14. An evaluation of the toxicological aspects and potential doses from the inhalation of coal combustion products.

    PubMed

    Liberda, Eric N; Chen, Lung Chi

    2013-06-01

    This paper reviews toxicological literature pertaining to coal combustion products (CCPs) inhalation and presents case studies on the inhalation of CCPs from the Kingston Fossil Plant area and from the Colbert Fossil Plant CCP landfill site. While most research regarding coal plant emissions focuses on fly ash, this article takes a holistic approach to examining not only emitted particulate matter such as fly ash, but also the theoretical calculated doses of landfilled CCPs. Furthermore, these doses are compared to in vitro and in vivo studies in order to highlight differences between laboratory-based studies and to emphasize the difficulty in extrapolating effects from inhalation exposures. In both case studies, fugitive emissions from the Kingston ash spill or the Colbert CCP-handling operations did not exceed any national ambient air quality standards or reference concentrations for individual components. Adverse effects such as mild pulmonary inflammation noted in the reviewed literature were in response to doses much higher than would be likely to occur in humans exposed to landfilled CCPs. We conclude that the doses for fugitive emissions calculated herein do not appear to be high enough to elicit a measurable adverse response in humans.

  15. Local versus total systemic bioavailability of beclomethasone dipropionate CFC and HFA metered dose inhaler formulations.

    PubMed

    Harrison, Lester I

    2002-01-01

    For inhaled formulations, the balance between desired local effects and undesired systemic activity can be expressed by L/T, where L represents bioavailability of drug from the lungs and T represents total systemic bioavailability. L/T is most useful when comparing formulations of the same inhaled substance. A high L/T is desirable as this implies efficient drug delivery to the target site, and minimization of unwanted activity from non-targeted drug delivery. The objective of this publication is to compare L/T for CFC and HFA inhaler formulations of beclomethasone dipropionate (BDP). Predictions of the L/T comparison were tested with clinical trials. From five deposition and pharmacokinetic studies, L/T ratios for CFC-BDP and HFA-BDP were calculated as 0.21 and 0.92, respectively. These ratios predicted two differences for the therapeutic use of these products: (1) a smaller dose of HFA-BDP than CFC-BDP may be required for efficacy; and (2) a smaller number of adverse events may be observed for the HFA-BDP product, when delivered at the equivalent dose, compared to the CFC comparitor. A dose-response study confirmed that less than half the dose of HFA-BDP is needed to give the same efficacy as CFC-BDP. Two safety studies that measured adrenal suppression demonstrated less suppression with HFA-BDP than with a comparable efficacious dose of CFC-BDP. It is concluded that L/T is a useful parameter that incorporates the systemic contributions of lung deposition and pharmacokinetics. It is recommended that this parameter be considered whenever deposition and pharmacokinetic data for two formulations of the same inhaled substance are compared.

  16. Pharmacokinetics and Safety of Single-Dose Inhaled Loxapine in Children and Adolescents.

    PubMed

    Selim, Sally; Riesenberg, Robert; Cassella, James; Kunta, Jeevan; Hellriegel, Edward; Smith, Mark A; Vinks, Alexander A; Rabinovich-Guilatt, Laura

    2017-10-01

    This multisite open-label study sought to characterize the pharmacokinetics and safety of a single dose of inhaled loxapine in children and adolescents. Loxapine powder for oral inhalation was administered via a single-use handheld drug device to children and adolescents (aged 10-17 years) with any condition warranting chronic antipsychotic use. Patients were dosed according to body weight and cohort (<50 kg [n = 15], 2.5 or 5 mg; ≥50 kg [n = 15], 5 or 10 mg); the first 6 patients (cohort 1) enrolled in each weight group received the lower dose. Patients were enrolled in the higher-dose group (cohort 2) after an interim pharmacokinetic and safety analysis of data from cohort 1. Blood samples were collected for 48 hours after dosing to determine the pharmacokinetic profile of loxapine and its metabolites. Safety was assessed using adverse event (AE), laboratory value, physical/neurologic examination, vital sign, electrocardiogram, suicidality, and extrapyramidal symptom assessment. Thirty patients were enrolled and evaluable for pharmacokinetics. Loxapine plasma concentrations peaked by 2 to 5 minutes in most patients; systemic exposure increased with dose in both weight subgroups. Loxapine terminal elimination half-life was ∼13 to 17 hours. The most common AEs were sedation and dysgeusia. Sedation was severe in 1 patient in the <50-kg group (2.5-mg dose) and 1 patient in the ≥50-kg group (5-mg dose). No AEs indicative of bronchospasm or other serious AEs were reported. Inhaled loxapine was rapidly absorbed and generally well tolerated in pediatric patients; no new safety signals were observed. © 2017, The American College of Clinical Pharmacology.

  17. A Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time

    DTIC Science & Technology

    2015-06-01

    USAMRICD‐TR‐15‐02  A Histological Assessment of Lung Injury in Rats  Exposed to Inhaled  Sulfur  Mustard across Dose  and Time    Derron A...Lung Injury in rats Exposed to Inhaled Sulfur Mustard across Dose and Time 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time 5a. CONTRACT NUMBER 5b. GRANT NUMBER   5c

  18. High-dose inhaled corticosteroids or addition of theophylline in patients with poorly controlled asthma?

    PubMed

    Celis, Pilar; Rada, Gabriel

    2015-08-19

    There are several management strategies for patients with poorly controlled asthma despite usual treatment. Increasing doses of inhaled corticosteroids or adding theophylline are among the therapeutic alternatives. However, the latter is associated with important adverse effects. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether theophylline or high-dose inhaled corticosteroids constitute a better alternative for symptomatic control or reduction in exacerbations in poorly controlled asthmatic patients because the certainty of the evidence is very low.

  19. Instant velocity and consistency of emitted cloud change by the different levels of canister filling with Metered Dose Inhalers (MDIs), but not with Soft Mist Inhalers (SMIs): a bench study.

    PubMed

    Dal Negro, Roberto W; Longo, Pietro; Ziani, Orestepaolo Villanis; Bonadiman, Luca; Turco, Paola

    2017-01-01

    Inhalation is the preferred route for respiratory drug delivery, but several factors contribute to the variability of the respirable dose fraction. Instant velocity and the dynamic characteristics of the droplet cloud represent crucial factors. Aim was to measure and compare the instant velocity and the consistency of emitted cloud from five different MDIs (A - Salbutamol sulphate 100mcg, GSK; B - Salbutamol sulphate 100mcg, Valeas; C - Salmeterol xinafoate/Fluticasone propionate 25/125mcg, GSK; D - Formoterol fumarate/Bechlomethasone propionate 6/100mcg, Chiesi; E - Formoterol fumarate/Fluticasone dipropionate 5/125mcg, Mundipharma) and one SMI (Tiotropium bromide 5mcg, Boehringer Ingelheim), at different distance from the nozzle and canister filling. Measurements were made at 90, 50, and 10% of canister filling, and at 5, 10, and 20 cm from the nozzle, for a total of 972 puffs. A high speed video photography protocol was adopted and high speed cameras (1.200 frames/sec.) were used. Data were acquired by means of specialized softwares. Temperature, humidity, and vibrations occurrence were strictly controlled during measurements. Statistics: Anova and p < 0.05 were accepted as the minimum significance level. MDIs generated different Instant velocities: MDI B generated the highest, while MDI A the lowest. As expected, velocity decreased in proportion to the distance from the nozzle. Except with MDI C, instant velocity decreased significantly over the first 50% of canister emptying, but dropped by >33% at 90% of emptying with all other MDIs (p < 0-037; p < 0.001; p < 0.005, and p < 0.001, respectively). Instant velocity was extremely lower (p < 0.001) and constant for all levels of canister filling (p = ns) with SMI. All MDIs had a very fast jet phase, ranging 0.01-0.03 s at 10 cm, and 0.03-0.05 s at 20 cm from the nozzle, without any significant difference from each other (p = ns). MDIs generated a cloud similarly tight (p

  20. Single- and multiple-dose pharmacokinetics of inhaled indacaterol in healthy Chinese volunteers.

    PubMed

    Jiang, Ji; Li, Lilly; Yin, Hequn; Woessner, Ralph; Emotte, Corinne; Li, Ruobing; Khindri, Sanjeev; Pei, Hu

    2015-06-01

    Indacaterol is an inhaled, ultra-long-acting β2-agonist that provides 24-h bronchodilation with once-daily dosing in patients with chronic obstructive pulmonary disorder. This study evaluated the pharmacokinetics, safety, and tolerability of multiple daily inhaled doses of indacaterol 150 or 300 μg once daily in healthy Chinese volunteers. This was a single-center, randomized, double-blind, multiple-dose, parallel-group study, placebo-controlled trial including two doses of indacaterol: 150 and 300 μg. Serum indacaterol was quantified using high-performance liquid chromatography-mass spectrometry with a lower limit of quantification of 0.01 ng/mL. The pharmacokinetic parameters were analyzed using non-compartmental analysis and included C max, T max, and AUC0-24h on Day 1 and AUC0-24h,ss, C max,ss, C min,ss, C av,ss, T max,ss, T 1/2, T 1/2,acc, CL/F, V z/F, and R acc on Day 14 (after repeated once-daily doses). Safety analyses were recorded using physical examination, biochemical tests, and ECG. Indacaterol steady state was achieved after 12-14 days of daily dosing. The mean effective half-life of indacaterol (based on drug accumulation at steady state) was 33.9 and 35.8 h for 150 and 300 μg, respectively. Systemic exposure to indacaterol increased 1.27 and 1.34-fold between the 150- and 300-μg doses on Day 1 (first dose) and Day 14 (repeated dose), respectively. Indacaterol 150 and 300 μg were safe and well tolerated in these volunteers. The pharmacokinetics of multiple inhaled doses of indacaterol 150 and 300 μg (for 14 days) were consistent with moderate systemic accumulation at steady state after repeated once-daily inhalation in healthy Chinese volunteers.

  1. Humidity affects the morphology of particles emitted from beclomethasone dipropionate pressurized metered dose inhalers.

    PubMed

    Ivey, James W; Bhambri, Pallavi; Church, Tanya K; Lewis, David A; McDermott, Mark T; Elbayomy, Shereen; Finlay, Warren H; Vehring, Reinhard

    2017-03-30

    The effects of propellant type, cosolvent content, and air humidity on the morphology and solid phase of the particles produced from solution pressurized metered dose inhalers containing the corticosteroid beclomethasone dipropionate were investigated. The active ingredient was dissolved in the HFA propellants 134a and 227ea with varying levels of the cosolvent ethanol and filled into pressurized metered dose inhalers. Inhalers were actuated into an evaporation chamber under controlled temperature and humidity conditions and sampled using a single nozzle, single stage inertial impactor. Particle morphology was assessed qualitatively using field emission scanning electron microscopy and focused ion beam-helium ion microscopy. Drug solid phase was assessed using Raman microscopy. The relative humidity of the air during inhaler actuation was found to have a strong effect on the particle morphology, with solid spheroidal particles produced in dry air and highly porous particles produced at higher humidity levels. Air humidification was found to have no effect on the solid phase of the drug particles, which was predominantly amorphous for all tested formulations. A critical level of air relative humidity was required to generate porous particles for each tested formulation. This critical relative humidity was found to depend on the amount of ethanol used in the inhaler, but not on the type of propellant utilized. The results indicate that under the right circumstances water vapor saturation followed by nucleated water condensation or ice deposition occurs during particle formation from evaporating propellant-cosolvent-BDP droplets. This finding reveals the importance of condensed water or ice as a templating agent for porosity when particle formation occurs at saturated conditions, with possible implications on the pharmacokinetics of solution pMDIs and potential applications in particle engineering for drug delivery.

  2. Bronchodilators delivered by nebuliser versus pMDI with spacer or DPI for exacerbations of COPD.

    PubMed

    van Geffen, Wouter H; Douma, W R; Slebos, Dirk Jan; Kerstjens, Huib A M

    2016-08-29

    Bronchodilators are a central component for treating exacerbations of chronic obstructive pulmonary disease (COPD) all over the world. Clinicians often use nebulisers as a mode of delivery, especially in the acute setting, and many patients seem to benefit from them. However, evidence supporting this choice from systematic analysis is sparse, and available data are frequently biased by the inclusion of asthma patients. Therefore, there is little or no formal guidance regarding the mode of delivery, which has led to a wide variation in practice between and within countries and even among doctors in the same hospital. We assessed the available randomised controlled trials (RCTs) to help guide practice in a more uniform way. To compare the effects of nebulisers versus pressurised metered dose inhalers (pMDI) plus spacer or dry powder inhalers (DPI) in bronchodilator therapy for exacerbations of COPD. We searched the Cochrane Airways Group Trial Register and reference lists of articles up to 1 July 2016. RCTs of both parallel and cross-over designs. We included RCTs during COPD exacerbations, whether measured during hospitalisation or in an outpatient setting. We excluded RCTs involving mechanically ventilated patients due to the different condition of both patients and airways in this setting. Two review authors independently assessed studies for inclusion, extracted data and assessed the risk of bias. We report results with 95% confidence intervals (CIs). This review includes eight studies with a total of 250 participants comparing nebuliser versus pMDI plus spacer treatment. We identified no studies comparing DPI with nebulisers. We found two studies assessing the primary outcome of 'change in forced expiratory volume in one second (FEV1) one hour after dosing'. We could not pool these studies, but both showed a non-significant difference in favour of the nebuliser group, with similar frequencies of serious adverse events. For the secondary outcome, 'change in FEV1

  3. Radiation dose to upper airways from inhaled oxygen-15 carbon dioxide

    SciTech Connect

    Meyer, E.; Yamamoto, L.Y.; Evans, A.C.; Tyler, J.L.; Diksic, M.; Feindel, W.

    1987-02-01

    According to Powell et al., significant retention of 15O in the tracheal mucosa results in a radiation absorbed dose of 75 to 200 rad upon breathing of 15O-CO/sub 2/ for one hour at 1 mCi/liter. Such a high dose would seriously compromise the 15O-CO/sub 2/ inhalation method for positron emission tomographic (PET) measurement of cerebral blood flow (CBF). In order to verify these results, we have assayed 15O activity in the tracheal region of three volunteers by PET during inhalation of 15O-CO/sub 2/ and 15O-O/sub 2/. Using methods similar to those of the above authors for estimating absorbed dose in the tracheal mucosa, we have obtained a value of 14-38 rad, which is more in keeping with 3-5 rad found by Bigler et al. from direct assay of mucus and saliva. We conclude that the 15O-CO/sub 2/ inhalation method is a safe and practical means of measuring CBF by PET.

  4. MDI versus Nebulizers for Acute Asthma

    PubMed Central

    Raissy, Hengameh H.; Kelly, H. William

    2004-01-01

    OBJECTIVE: To evaluate studies comparing metered dose inhalers with holding chambers to nebulizers in the emergency department for the treatment of asthma exacerbation. DATA SOURCE: Primary articles and systematic review provided by the Cochrane Airways Review Group of the Cochrane Library identified by MEDLINE search (1966–February 2004) and through secondary sources. DATA SYNTHESIS: The Cochrane review included 21 randomized clinical trials conducted in hospital emergency departments comparing clinical outcomes following β2 agonist administration via a nebulizer or a metered dose inhaler with holding chamber. Although the relative risk ratio of hospital admission with metered dose inhaler and holding chamber did not differ in children or in adults compared to the nebulizer delivery, none of the individual studies reviewed were powered to detect a difference in the rate of hospital admission. Specific factors in the treatment of acute asthma such as assessment of severity, appropriate outcome selection, appropriate dose selection, and appropriate delivery systems need to be considered to critically evaluate the literature. CONCLUSION: Although available randomized clinical trials suggest equivalency of metered dose inhaler plus holding chambers and nebulized delivery of inhaled β2 agonists, these trials are biased to show no difference in response. There is no data to support the advantage of one method over the other in mild to moderate asthmatic patients either clinically or economically. PMID:23118701

  5. Dose-proportional pharmacokinetics of budesonide inhaled via Turbuhaler®

    PubMed Central

    Kaiser, H; Aaronson, D; Dockhorn, R; Edsbäcker, S; Korenblat, P; Källén, A

    1999-01-01

    Aims The present pharmacokinetic study was undertaken to determine the dose proportionality of three different doses of budesonide—400 μg, 800 μg or 1600 μg administered twice daily by a dry-powder inhaler (Turbuhaler®) in adult patients with mild asthma. Methods A total of 38 patients received budesonide by inhalation, 13 received 400 μg twice daily, 12 received 800 μg twice daily and 13 received 1600 μg twice daily. Mean FEV1 at inclusion was 3.4, 4.0 and 3.9 l min−1 in the three groups, respectively. Blood samples were taken after a single dose, and after 3 weeks of daily treatment, for pharmacokinetic evaluation. Plasma concentrations of budesonide were determined by liquid chromatography plus mass spectrometry. Results Eleven evaluable patients remained in each dose group. Mean time to peak budesonide plasma concentration (tmax) was short (0.28–0.40 h) and did not differ between treatment groups. Budesonide concentrations declined rapidly thereafter, indicating efficient pulmonary absorption and rapid elimination with a half-life of approximately 3 h. Cmax was 1.4(2.0) nmol l−1 (single (repeated) doses), 2.6(3.6) nmol l−1 and 5.4(6.4) nmol l−1 after 400, 800 and 1600 μg twice daily, respectively. The corresponding results for the area under the plasma concentration vs time curve (AUC) were 271(325), 490(628) and 915(1096) nmol l−1 min. Ninety percent confidence intervals for pairwise dose-normalized Cmax and AUC comparisons between groups were large but contained unity in all cases, thus indicating dose-proportional pharmacokinetics. Regression on analysis supported these findings. Mean AUC after repeated doses (AUC(0,12 h,RD)) was on average 23% higher than the mean AUC after single doses (AUC(0,∞,SD)(P = 0.04) with no significant differences between doses, indicating slight accumulation following bid dosing. Conclusions In this relatively small study, budesonide inhaled via Turbuhaler® appeared to have dose

  6. 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...

  7. 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...

  8. Relative lung deposition of salbutamol following inhalation from a spacer and a Sidestream jet nebulizer following an acute exacerbation.

    PubMed

    Mazhar, Syed H R; Ismail, Nahlah E; Newton, Duncan A G; Chrystyn, Henry

    2008-03-01

    What is already known about this subject. Studies have shown that a large volume spacer attached to a metered dose inhaler provides similar bronchodilator effects to nebulized dosing during the management of patients following an acute exacerbation. Due to the high doses used, these effects could be measured at the top of the dose-response relationship and the response limited due to the patient's exacerbation. Although clinical end-points are the gold standard to show comparability, some indication of similar lung deposition is useful to consolidate any claims. What this study adds. The urinary pharmacokinetic method we have used postinhalation provides an index of lung deposition for inhalation methods that can be incorporated into the routine management of patients with an acute exacerbation. This is the first study to identify and compare lung deposition and systemic delivery for inhalation methods within the setting of the routine management of asthma and chronic obstructive pulmonary disease patients following hospitalization due to an acute exacerbation. The study highlights the comparability of the doses for the two inhalation methods evaluated with respect to lung deposition, systemic delivery and bronchodilator response. Studies comparing inhalation methods in acute exacerbations have not assessed lung deposition. Five 100-mug salbutamol doses were inhaled from a metered dose inhaler plus spacer (MDI + SP) and 5 mg was nebulized (NEB) following acute exacerbation hospitalization. Urinary salbutamol excretion was determined at 30 min (USAL0.5) and over 24 h (USAL24) postinhalation together with forced expiratory volume in 1 s (FEV(1)). The USAL0.5 mean ratio (90% confidence interval) post MDI + SP and NEB [n = 19 asthma, 11 chronic obstructive pulmonary disease (COPD)] was 1.01 (0.81, 1.26). USAL24 was less (P < 0.001) following MDI + SP, whereas FEV(1) was similar. Only a small difference between asthmatics and COPD patients was observed for the MDI + SP

  9. 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

  10. 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.

  11. Add-on LABA in a separate inhaler as asthma step-up therapy versus increased dose of ICS or ICS/LABA combination inhaler

    PubMed Central

    Colice, Gene; Israel, Elliot; Roche, Nicolas; Postma, Dirkje S.; Guilbert, Theresa W.; van Aalderen, Willem M.C.; Grigg, Jonathan; Hillyer, Elizabeth V.; Thomas, Victoria; Martin, Richard J.

    2016-01-01

    Asthma management guidelines recommend adding a long-acting β2-agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12–80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point in comparisons of cohorts matched for asthma severity and control during the baseline year. After 1:2 cohort matching, the increased extrafine ICS versus separate ICS+LABA cohorts included 3232 and 6464 patients, respectively, and the fine-particle ICS/LABA FDC versus separate ICS+LABA cohorts included 7529 and 15 058 patients, respectively (overall mean age 42 years; 61–62% females). Over one outcome year, adjusted OR (95% CI) for achieving asthma control were 1.25 (1.13–1.38) for increased ICS versus separate ICS+LABA and 1.06 (1.05–1.09) for ICS/LABA FDC versus separate ICS+LABA. For patients with asthma, increased dose of extrafine-particle ICS, or add-on LABA via ICS/LABA combination inhaler, is associated with significantly better outcomes than ICS+LABA via separate inhalers. PMID:27730200

  12. 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.

  13. 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

  14. Randomized, dose-ranging study of a fluticasone propionate multidose dry powder inhaler in adolescents and adults with uncontrolled asthma not previously treated with inhaled corticosteroids.

    PubMed

    Kerwin, Edward M; Gillespie, Michael; Song, Sharon; Steinfeld, Jonathan

    2017-01-02

    A novel, inhalation-driven, multidose dry powder inhaler (MDPI) eliminates the need to coordinate actuation with inhalation. To characterize dose response, efficacy, and safety of fluticasone propionate (Fp) MDPI, a dose-ranging study was conducted with placebo and active comparators. This 12-week, double-blind, parallel-group study randomized patients aged ≥12 years with uncontrolled persistent asthma not previously treated with inhaled corticosteroid therapy (N = 622) to twice-daily treatment with Fp MDPI (12.5, 25, 50, or 100 µg), placebo MDPI, or open-label Fp dry powder inhaler (DPI) 100 µg. The primary efficacy endpoint was change from baseline over 12 weeks in trough (morning pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1). Blood samples were collected from a patient subset to evaluate pharmacokinetics. Adverse events were monitored. Fp MDPI 25, 50, and 100 µg significantly improved change from baseline in trough FEV1 over 12 weeks compared with placebo (p < 0.01). There were no substantial differences in FEV1 change from baseline over 12 weeks between any Fp MDPI dose and Fp DPI 100 µg. Maximum observed concentration (Cmax) of Fp increased with increasing Fp MDPI doses; time of Cmax was similar across doses and treatments. Systemic exposures for Fp MDPI 25 and 50 µg were lower than that for Fp DPI 100 µg. The safety profile of Fp MDPI was consistent with that of Fp DPI. In this study, Fp MDPI 25 and 50 µg provided comparable efficacy and safety to Fp DPI 100 µg, with lower systemic exposure.

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. [Specific parameters for the calculation of dose after aerosol inhalation of transuranium elements].

    PubMed

    Ramounet-Le Gall, B; Fritsch, P; Abram, M C; Rateau, G; Grillon, G; Guillet, K; Baude, S; Bérard, P; Ansoborlo, E; Delforge, J

    2002-07-01

    A review on specific parameter measurements to calculate doses per unit of incorporation according to recommendations of the International Commission of Radiological Protection has been performed for inhaled actinide oxides. Alpha activity distribution of the particles can be obtained by autoradiography analysis using aerosol sampling filters at the work places. This allows us to characterize granulometric parameters of "pure" actinide oxides, but complementary analysis by scanning electron microscopy is needed for complex aerosols. Dissolution parameters with their standard deviation are obtained after rat inhalation exposure, taking into account both mechanical lung clearance and actinide transfer to the blood estimated from bone retention. In vitro experiments suggest that the slow dissolution rate might decrease as a function of time following exposure. Dose calculation software packages have been developed to take into account granulometry and dissolution parameters as well as specific physiological parameters of exposed individuals. In the case of poorly soluble actinide oxides, granulometry and physiology appear as the main parameters controlling dose value, whereas dissolution only alters dose distribution. Validation of these software packages are in progress.

  18. Investigation of some commercially available spacer devices for the delivery of glucocorticoid steroids from a pMDI.

    PubMed

    Williams, R O; Patel, A M; Barron, M K; Rogers, T L

    2001-05-01

    Five commercially available spacers were investigated to determine their influence on the percentage of drug retained in the spacer device, percentage fine particle fraction (FPF), percentage deposited in the induction port, mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). Betamethasone valerate (BMV) and triamcinolone acetonide (TAA) were used as model drugs in the pressurized metered dose inhaler (pMDI) formulations containing the propellant HFA 134a. The BMV was dissolved in an ethanol/HFA 134a system, and the TAA was suspended in HFA 134a using ethanol as a dispersing agent. The metering chamber volume of the valve was either 50 microl or 150 microl. The spacer devices investigated included the ACE, Aerochamber, Azmacort, Easivent, and Ellipse spacers. Each spacer device was attached to an Andersen Cascade Impactor powered by a vacuum pump. Cascade impaction data were used to derive the percentage drug deposited in the induction port, MMAD, GSD, and FPF. The BMV particles emitted from the spacers were finer than the TAA particles because the dissolved drug precipitated as the cosolvent evaporated. The TAA particles had significantly larger MMADs because many undissolved drug particles were contained within each droplet following actuation. After evaporation of the liquid continuous phase, the suspended drug aggregated to form larger agglomerates than those particles precipitated from the BMV pMDI solution droplets. The addition of a spacer device lowered the MMAD to less than 4.7 microm for particles from both the BMV pMDI solution and the TAA pMDI suspension. The addition of a spacer device also lowered the percentage drug deposited in the induction port. The FPF was significantly increased when a spacer device was used. The MMAD significantly decreased when a spacer device was added for the two model drugs when using the 150-microl metering valves, but the difference was not statistically significant when the 50-microl valves

  19. (131)I age-dependent inhalation dose in Southern Poland from Fukushima accident.

    PubMed

    Brudecki, K; Szufa, K; Mietelski, J W

    2017-03-01

    A general method for calculating doses absorbed from isotopes released in nuclear accidents is presented. As an example, this method was used to calculate doses for inhabitants of Southern Poland due to inhalation of (131)I released due to the Fukushima nuclear plant accident. (131)I activity measurements in the air of that region provided the basis for the study. The proposed model is based on a complex biokinetic model for iodine merging the Leggett model developed in 2010 with the human respiratory tract and gastrointestinal tract models recommended by the International Commission on Radiological Protection (ICRP). This model is described here, and it is demonstrated that resulting dose estimates are consistent with those obtained using the ICRP methodology. Using the developed model, total doses were calculated for six age groups of both genders, for gaseous and aerosol fractions alike. The committed effective dose, H 50, for an adult man reached 16 nSv, which is lower than 0.001% of the background dose. The dose for the thyroid of an adult reached 0.33 μSv, which corresponds to circa 0.0007% of the dose to the population of Southern Poland after the Chernobyl nuclear plant accident.

  20. Dependence of dose coefficients for inhaled 239Pu on absorption parameters.

    PubMed

    Suzuki, K; Sekimoto, H; Ishigure, N

    2001-01-01

    With regard to dissolution of particles in the respiratory tract after inhalation, the International Commission on Radiological Protection (ICRP) has classified all radionuclides into only three types according to the chemical form of compounds, and default values of absorption parameters are proposed for each type. However, it is just a simplification to estimate doses for practical use, and there is a possibility of unfitness in such an assortment. A code has been developed to reproduce the ICRP's dose coefficients for 239Pu, which is one of the most important elements for occupational exposure. By using this code, the respective absorption parameters were modified, and the effect owing to these changes evaluated. It was shown consequently that changes of absorption parameters do not greatly influence the effective doses of 239Pu for workers.

  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. Particle deposition in spontaneously hypertensive rats exposed via whole-body inhalation: measured and estimated dose.

    PubMed

    Wichers, Lindsay B; Rowan, William H; Nolan, Julianne P; Ledbetter, Allen D; McGee, John K; Costa, Daniel L; Watkinson, William P

    2006-10-01

    A plethora of epidemiological studies have shown that exposure to elevated levels of ambient particulate matter (PM) can lead to adverse health outcomes, including cardiopulmonary-related mortality. Subsequent animal toxicological studies have attempted to mimic these cardiovascular and respiratory responses, in order to better understand underlying mechanisms. However, it is difficult to quantitate the amount of PM deposited in rodent lungs following inhalation exposure, thus making fundamental dose-to-effect assessment and linkages to human responses problematic. To address this need, spontaneously hypertensive rats were exposed to an oil combustion-derived PM (HP12) via inhalation while being maintained in whole-body plethysmograph chambers. Rats were exposed 6 h/day to 13 mg/m(3) of HP12 for 1 or 4 days. Immediately following the last exposure, rats were sacrificed and their tracheas and lung lobes harvested and separated for neutron activation analysis. Total lower respiratory tract deposition ranged from 20-60 microg to 89-139 microg for 1- and 4-day exposures, respectively. Deposition data were compared to default and rat-specific estimates provided by the Multiple Path Particle Deposition (MPPD) model, yielding model predictions that were < 33% of the measured dose. This study suggests that HP12 exposure decreased particle clearance, as the mass of HP12 in the lungs following a 4-day protocol was nearly four times that observed after a 1-day exposure. This work should improve the ability of risk assessors to extrapolate rat-to-human exposure concentrations on the basis of lung burdens and, thus, better relate inhaled doses and resultant toxicological effects.

  3. Pressurized metered dose inhalers: chlorofluorocarbon to hydrofluoroalkane transition-valve performance.

    PubMed

    Cummings, R H

    1999-12-01

    This article reviews the issues related to the performance of valves in metered dose inhalers with respect to chlorofluorocarbon propellant replacement. Reformulation of existing chlorofluorocarbon-based products with hydrofluoroalkane propellants has been a much more difficult task than initially anticipated, complicated by the need to concurrently develop better performing valves with cleaner extractive profiles. This paper will examine issues related to the reformulation and development of new valves and the tests and procedures used to evaluate valve performance. Evaluation of valve performance will consider the tests performed: mechanisms by which valves fail and analytic testing errors that can complicate the interpretation of results.

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

    DOE PAGES

    Viner, Brian J.; Jannik, Tim; Stone, Daniel; ...

    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. The 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. In conclusion, this approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.« less

  5. 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.

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

    PubMed Central

    Nicod, Laurent P.; Kohler, Malcolm

    2016-01-01

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

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

    PubMed

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

    2004-01-01

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

  8. Twenty years of HFA pMDI patents: facts and perspectives.

    PubMed

    Rogueda, Philippe; Lallement, Arthur; Traini, Daniela; Iliev, Ilian; Young, Paul M

    2012-09-01

     Over the past 20 years, the inhalation drug delivery industry has undergone a quiet revolution after the phasing out of the chlorofluorocarbon propellants used to formulate pressure-metered dose inhalers (pMDIs). This review looks back to the creative landscape of those 20 years through a study of patent application trends. To this end, an analysis of the hydrofluoroalkane pMDIs patent landscape was undertaken. A statistical analysis demonstrates that 20 years after the introduction of hydrofluoroalkanes in the inhalation delivery field, the original patent applications are coming to the end of their legal life. Detailed analysis revealed that, from a total of 971 of the patents identified, up to 2.3% will expire within the next 5 years, rising to up to 7.3% in the next 10 years. The UK and USA were the main patent destinations and locations of inventive activity, as measured by patent filing location. Interestingly, the UK was the first destination and location of inventive activity in Europe, largely due to the activity of GlaxoSmithKline, followed by Italy, thanks to the work of Trinity-Chiesi. The analysis also showed that patent assignees are not always major pharmaceutical companies, with suppliers of propellants, as well as companies without major inhalation activity (such as Novadel), making substantial contributions to the landscape. These developments may have a significant impact on innovation trends and key company activity around novel pMDI formulations, in particular for generics manufacturers. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  9. A comparative study of efficacy of salbutamol via metered dose inhaler with volumatic spacer and via dry powder inhaler, easyhaler, to nebulization in mild to moderate severity acute asthma exacerbation in childhood.

    PubMed

    Vangveeravong, Mukda

    2008-10-01

    Rapid-acting inhaled beta-2 agonist is standard treatment in acute asthmatic patient; it causes smooth muscle dilatation, gives rapid action and has less side effect compared with parenteral and oral form. There are many forms of inhaler including nebulization, MDI and DPI. In Thailand the most common form of salbutamol administration for the treatment of acute exacerbation of asthma is via nebulization. To compare the clinical effectiveness and side effects of salbutamol via MDI with Volumatic spacer and via DPI (Easyhaler), with nebulization in mild to moderate severity of acute asthma exacerbation in childhood. A prospective, randomized controlled study in children, aged 5- 18-years-old with mild to moderate severe asthmatic attack, is done at the Emergency Room, QSNICH during October 2004 to February 2006. These children with acute asthma attack are randomly-assigned to 3 groups of different salbutamol administrations: group 1 via nebulization, group 2 via MDI with volumatic spacer and group 3 via DPI (Easyhaler). Salbutamol is administered and clinical responses: asthma score, oxygen saturation, PR, RR, BP and side effects (tremor and palpitation) are recorded at 0, 20, 40 and 60 minutes after the drug administrations. The drug will be repeated every 20 minutes for the total maximum of 3 times. If there is no clinical improvement, they will be admitted to the hospital for further management. There are 54 asthmatic children, 35 male (64.8%) and 19 female (35.2%). Their mean age is 8.4 +/- 2.3 years. There are 18patients in each group. There is no significant difference in efficacy of salbutamol among the 3 groups as measured by asthma score, O2 saturation, PR, RR and BP Tremor are equally observed in all 3 groups (5.5%) while palpitation are observed in 11.1% of group 1 and 2 only. One patient in group 2 and 3 are admitted while no patient in group 1 is. Rapid-acting inhaled beta-2 agonist via MDI with volumatic spacer and DPI (Easyhaler) can be used

  10. Dose assessment for inhaling hafnium particles based on laboratory rats study.

    PubMed

    Zhou, Y; Cheng, Y S

    2003-04-01

    Internal radiation from inhalation of hafnium tritide aerosols may be a significant radiation protection problem encountered by nuclear facility workers. Based on experimental results of the rat intratracheally instilled with hafnium tritide particles and on a self-absorption factor of beta particles determined by a numerical method, a biokinetic model was developed for inhaled particles of hafnium tritide. Results show that lung burdens of the tritide are well represented by a two-component exponential equation; biological half-lives derived for the retention of 3H in lung were 4.9 d and 1,257 d for the short- and long-term clearance, respectively. The tritium clearance rate via urine or feces was described by bi-phase exponential components. At the end of the experiment (180 d after instillation), only approximately 30% of the initial lung burden of 3H had been eliminated, of which approximately 98% was excreted via feces and 2% in urine, but none through exhaled air. Results also showed that a large percentage (70%) of the hafnium tritide initially present in lung still remained in the organ 6 mo after the exposure. The calculation of the radiation dose indicates that the cumulative dose to the lung directly from the tritide particles was approximately 10(6) times the lung dose from the dissolved tritium in the lung region. The committed effective dose to the lung was estimated to be 5.41 x 10(-10) Sv Bq(-1), which is over 99% of that to the whole body. The dose to the liver was 6.00 x 10(-15) Sv Bq(-1). This information will be useful in developing new guidelines for radiation protection purposes.

  11. A randomized, placebo-controlled repeat-dose thorough QT study of inhaled loxapine in healthy volunteers

    PubMed Central

    Cassella, James V.; Spyker, Daniel A.; Yeung, Paul P.

    2015-01-01

    Objective: This randomized, double-blind, active- and placebo-controlled, crossover, thorough QT study assessed the effect of two inhaled loxapine doses on cardiac repolarization as measured by corrected QT (QTc) interval in healthy subjects (ClinicalTrials.gov NCT01854710). Methods: Subjects received two doses of inhaled loxapine (10 mg) 2 hours apart + oral placebo, two doses of inhaled placebo + oral placebo, or two doses of inhaled placebo + oral moxifloxacin (400 mg; positive control), with ≥ 3 days washout between treatments. Two-sided 90% confidence intervals (CIs) were calculated around least-squares mean predose placebo-subtracted individually corrected QT durations (ΔΔQTcIs) at 12 time points throughout 24 hours after dosing. A ΔΔQTcI 95% upper CI exceeding 10 msec was the threshold indicating QTc prolongation (primary endpoint). Secondary endpoints included Fridericia- and Bazett-corrected QT duration and QTcI outliers. Pharmacokinetics and adverse events (AEs) were also assessed. Results: Of 60 subjects enrolled (mean age, 33.8 years; 52% male), 44 completed the study. Post loxapine dosing, no ΔΔQTcI 95% upper CI exceeded 10 msec; the largest was 6.31 msec 5 minutes post dose 2. Methodology was validated by ΔΔQTcI 95% lower CIs exceeding 5 msec at 9 of 12 time points after moxifloxacin dosing. Loxapine plasma concentrations increased rapidly (mean Cmax, 177 ng/mL; median tmax 2 minutes after dose 2, 2.03 hours after dose 1). There were no deaths, serious AEs, or AEs leading to discontinuation, and one severe AE. Conclusions: Primary and secondary endpoints indicated two therapeutic doses of inhaled loxapine did not cause threshold QTc prolongation in this study. PMID:26501204

  12. 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.

  13. Ozone inhalation leads to a dose-dependent increase of cytogenetic damage in human lymphocytes.

    PubMed

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

    2015-05-01

    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 used 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 one MN per cell (P <  .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. © 2014 Wiley Periodicals, Inc.

  14. 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

  15. 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, ...

  16. 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, ...

  17. 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

    2006-03-09

    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.

  18. 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

  19. Formulation and Development of Metered Dose Inhalations of Salbutamol in Solution Form

    PubMed Central

    Khale, Anubha; Bajaj, Amrita

    2011-01-01

    In the present study attempts were made to prepare metered dose inhalation of salbutamol in solution form and compared it with the marketed metered dose inhalation in suspension form. Solution form of the drug was found better than marketed suspension formulation with respect to homogeneity and content uniformity. Propellant blend P-11 and P-12 in the proportion 30:70 was selected as it gave optimum vapour pressure. Surfactant oleic acid in concentration 10 mg per can was selected as it gave best results with clarity, spray pattern, vapour pressure, content per spray and rate of evaporation. Ethyl alcohol 2 ml per can was used as a cosolvent to give a clear solution, optimum vapour pressure, maximum content per spray and fair rate of evaporation. The selected formulation was subjected to the physico-chemical evaluation tests as per the standard pharmacopoeial procedures and the characteristics of the formulations were further compared with a conventional marketed formulation. In vitro study reveled the net respirable fraction was better than marketed preparation. PMID:22923867

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

    PubMed Central

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

    2016-01-01

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

  1. Investigation of multiphase multicomponent aerosol flow dictating pMDI-spacer interactions.

    PubMed

    Sarkar, Saurabh; Peri, S Prasad; Chaudhuri, Bodhisattwa

    2017-08-30

    The use of Pressurized metered dose inhalers (pMDIs) for the treatment of asthma and other chronic obstructive pulmonary diseases is frequently associated with breath-actuation synchronization problems and poor pulmonary delivery, particularly amongst the pediatric and geriatric population groups. Spacers, or Valved Holding Chambers (VHCs), are frequently used to address these problems. However, the performance of spacers with different pMDIs is also highly variable and needs to be investigated. The purpose of the current study is to develop a computational fluid dynamics (CFD) model which can characterize multiphase multicomponent aerosol flow issuing from a commercial suspension-based pMDI into a spacer. The CFD model was initially calibrated against published experimental measurements in order to appropriately model the spray characteristics. This model was subsequently used to examine several combinations of inhaler, spacer and USP Throat geometries under different discharge rates of coflow air. The CFD model predictions compared favorably with experimental measurements. In particular, the predictions show, in accordance with experimental determinations, a decrease of drug retained by the spacers with increasing coflow air. The recirculation observed near the obstructions in axial path of the spray within either spacer is considered to be central for increasing spray retention and drug deposition behavior. Fluid flow patterns within the spacers were correlated with drug deposition behavior through a dimensionless variable, the Recirculation index (RCI). Bigger particles were found to be selectively retained within the spacer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Primary aspergillosis of vocal cord: Long-term inhalational steroid use can be the miscreant.

    PubMed

    Saha, Arpita; Saha, Kaushik; Chatterjee, Uttara

    2015-12-01

    Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as a part of systemic infection in immunocompromised patients. A case of vocal cord aspergillosis with no systemic extension in an immunocompetent patient on long-term steroid metered dose inhaler (MDI) is presented here, because of its rarity. The present case is a 28-year-old asthmatic female who was on inhalational steroid for 8 years, presented with sudden onset of severe dysphonia for 5 days. Fiberoptic laryngoscopy demonstrated whitish plaque involving right vocal cord, clinically suggestive of fungal laryngitis. Microlaryngeal laser surgery was performed with stripping of the plaque. Histopathology demonstrated ulcerated hyperplastic squamous epithelium with masses of fungal hyphae, which was confirmed to be Aspergillus species on fungal culture. This rare but serious adverse effect of long-term steroid MDI use must be kept in mind while treating an asthmatic patient. We also present a brief review of literature of laryngeal aspergillosis.

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

    PubMed

    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.

  4. [Salbutamol in asthma treatment: with nebulizer or inhaler?].

    PubMed

    Cavkaytar, Ozlem; Sekerel, Bülent Enis

    2012-01-01

    Breath relieving and protective drugs in asthma treatment are applied through pressurized metered dose inhaler (pMDI), nebulizer or dry powder inhaler. The short acting beta-2 agonist salbutamol used in acute asthma exacerbation is found in the forms of nebule or pMDI in Turkey. Nebule form is used more frequently in emergency services. The aim of this review is to compare these two routes of administration through clinical efficacy, the amount of drug reaching to the lungs and adverse events comprehensively by way of looking through the studies. Additionally effect of different inhalation techniques through chambers, different methods used in cleaning of them and different types of nebulizers, to the efficacy are investigated. As a result, asthma exacerbation can be treated with pMDIs used through holding chambers in emergency room successfully when applied with dosing scheme appropriate for the patient's age, weight and severity of exacerbation (usually 1/4th of nebule dosing) on the contrary to ordinary method of nebulizers.

  5. A review of the development of Respimat Soft Mist Inhaler.

    PubMed

    Dalby, R; Spallek, M; Voshaar, T

    2004-09-28

    Respimat Soft Mist Inhaler (SMI) is a new generation inhaler from Boehringer Ingelheim developed for use with respiratory drugs. The device functions by forcing a metered dose of drug solution through a unique and precisely engineered nozzle (the uniblock), producing two fine jets of liquid that converge at a pre-set angle. The collision of these two jets generates the soft mist. The soft mist contains a high fine particle fraction of approximately 65 to 80%. This is higher than aerosol clouds from conventional portable inhaler devices, such as pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). In addition, the relatively long generation time of the aerosol cloud (approximately 1.5s) facilitates co-ordination of inhalation and actuation--a major problem with pMDIs. These features, together with the slow velocity of the soft mist, result in larger amounts of the drug reaching the lungs and less being deposited in the oropharynx compared with either pMDIs or DPIs. Generation of the soft mist from Respimat SMI is purely mechanical, so propellants are not necessary. The innovative design of Respimat SMI, using water-based drug formulations, ensures patients receive consistent and reliable doses of the drug with each actuation. The device was initially tested in scintigraphic lung deposition studies and produced encouraging results when compared with the chlorofluorocarbon-based pMDI (CFC-MDI). Subsequent clinical studies have confirmed that Respimat SMI is effective and safe in delivering bronchodilators to patients with asthma or chronic obstructive pulmonary disease.

  6. [Deliberate interruptions and changes of dose of inhaled corticosteroids by asthma patients: "a community pharmacy study"].

    PubMed

    Laforest, L; Van Ganse, É; Devouassoux, G; Chatté, G; Tamberou, C; Belhassen, M; Chamba, G

    2015-01-01

    Adherence to inhaled corticosteroids (ICS) remains a major issue for asthma management, even among patients receiving a regular prescription from their doctor. The frequency of deliberate interruption of ICS, and of spontaneous changes of dose, were studied in a population of asthma patients recruited in community pharmacies. Asthma patients (aged 18-50) recruited in community pharmacies reported in self-administered questionnaires their spontaneous interruptions and changes of doses of ICS during the past 3 months. The characteristics of patients who interrupted their therapy or who modified the dose were compared with other patients. The studied population included 252 patients (mean age 35 year-old, females: 59%), of whom 62% had inadequately controlled asthma. Among these patients, 25% had interrupted ICS therapy during the past 3 months, while 21% spontaneously changed the dose. The most reported reason for interrupting ICS was the cessation of symptoms (50%). In multivariate analysis, interrupting ICS was mainly associated with inadequate asthma control (OR=3.1, 95% CI 1.5-6.4), while the strongest association with changing ICS doses was the patients' perception of asthma as a concern in their lives (OR=3.2, 95% CI 1.2-8.4). These results underline a poor understanding of the purpose of ICS therapy by patients. They also highlight the need of therapeutic education to improve the management of the disease. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  7. Computational fluid dynamics (CFD) assisted performance evaluation of the Twincer™ disposable high-dose dry powder inhaler.

    PubMed

    de Boer, Anne H; Hagedoorn, Paul; Woolhouse, Robert; Wynn, Ed

    2012-09-01

    To use computational fluid dynamics (CFD) for evaluating and understanding the performance of the high-dose disposable Twincer™ dry powder inhaler, as well as to learn the effect of design modifications on dose entrainment, powder dispersion and retention behaviour. Comparison of predicted flow and particle behaviour from CFD computations with experimental data obtained with cascade impactor and laser diffraction analysis. Inhaler resistance, flow split, particle trajectories and particle residence times can well be predicted with CFD for a multiple classifier based inhaler like the Twincer™. CFD computations showed that the flow split of the Twincer™ is independent of the pressure drop across the inhaler and that the total flow rate can be decreased without affecting the dispersion efficacy or retention behaviour. They also showed that classifier symmetry can be improved by reducing the resistance of one of the classifier bypass channels, which for the current concept does not contribute to the swirl in the classifier chamber. CFD is a highly valuable tool for development and optimisation of dry powder inhalers. CFD can assist adapting the inhaler design to specific physico-chemical properties of the drug formulation with respect to dispersion and retention behaviour. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  8. 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.

  9. Lack of awareness of need to clean CFC-free metered-dose inhalers.

    PubMed

    Slader, Cassandra A; Reddel, l Helen K; Bosnic-Anticevich, Sinthia Z

    2004-01-01

    Chlorofluorocarbon (CFC)-free metered-dose inhalers (MDIs) were introduced into Australia in 1999. Device care instructions were modified (e.g., CFC-free salbutamol inhalers to be washed weekly), but this information was not communicated directly to health care professionals. This pilot study aimed to assess the level of awareness of device care protocols for CFC-free MDIs by patients and their pharmacists. Purchasers of CFC-free MDIs were recruited from four community pharmacies. They were interviewed regarding information sources, knowledge of propellant change, and awareness of and adherence to device care protocols. The dispensing pharmacists were interviewed for knowledge of CFC-free device care. The primary outcome variable was awareness of the relevant device care protocol. Thirty-nine patients were interviewed. Most patients (77%) were aware of the change to CFC-free propellant. Only nine patients (23%) were aware of the need to wash the device holder, and four patients (10% of total) complied with the specified protocol. One of the ten dispensing pharmacists could describe correct device care protocols for the CFC-free MDIs. Although most patients are aware that MDIs are now CFC-free, there is a low level of awareness of the device care required for these inhalers, and a very low rate of compliance with recommended practice. Although the clinical impact of failing to wash the device holder is unclear, this added instruction may have substantial implications for patient satisfaction and medication delivery. Pharmaceutical manufacturers need to highlight to health care professionals any clinically important changes in device care instructions, so that appropriate information may be passed on to patients.

  10. 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

  11. Evaluating the technique of using inhalation device in COPD and bronchial asthma patients.

    PubMed

    Arora, Piyush; Kumar, Lokender; Vohra, Vikram; Sarin, Rohit; Jaiswal, Anand; Puri, M M; Rathee, Deepti; Chakraborty, Pitambar

    2014-07-01

    In asthma management, poor handling of inhalation devices and wrong inhalation technique are associated with decreased medication delivery and poor disease control. The key to overcome the drawbacks in inhalation technique is to make patients familiar with issues related to correct use and performance of these medical devices. The objective of this study was to evaluate and analyse technique of use of the inhalation device used by patients of COPD and Bronchial Asthma. A total of 300 cases of BA or COPD patients using different types of inhalation devices were included in this observational study. Data were captured using a proforma and were analysed using SPSS version 15.0. Out of total 300 enrolled patients, 247 (82.3%) made at least one error. Maximum errors observed in subjects using MDI (94.3%), followed by DPI (82.3%), MDI with Spacer (78%) while Nebulizer users (70%) made least number of errors (p = 0.005). Illiterate patients showed 95.2% error while post-graduate and professionals showed 33.3%. This difference was statistically significant (p < 0.001). Self-educated patients committed 100% error, while those trained by a doctor made 56.3% error. Majority of patients using inhalation devices made errors while using the device. Proper education to patients on correct usage may not only improve control of the symptoms of the disease but might also allow dose reduction in long term. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Enantioselective disposition of (R)-salmeterol and (S)-salmeterol in urine following inhaled dosing and application to doping control.

    PubMed

    Jacobson, Glenn A; Hostrup, Morten; Narkowicz, Christian K; Nichols, David S; Haydn Walters, E

    2016-11-07

    Salmeterol (USAN, INN, BAN) is a long-acting beta2-adrenoceptor agonist (LABA) widely used in the treatment of airways disease. Although salmeterol is permitted via inhalation by athletes and supratherapeutic dosing may enhance performance, no urine threshold has been established by the World Anti-Doping Agency (WADA). Salmeterol is a chiral compound consisting of (R)- and (S)-enantiomers, normally administered as racemic (rac-) mixture via inhalation. Levels of rac-salmeterol in urine are often below detectable levels and there is surprisingly little information regarding the enantioselectivity of salmeterol pharmacokinetics. In this study, subjects inhaled either 50 (n = 6) or 200 µg (n = 4; generally regarded as maximum therapeutic dose) of salmeterol and urine was then collected for 24 h and analyzed by enantioselective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Maximum rac-salmeterol urine concentrations were obtained at 2 h for both doses with medians of 0.084 ng/mL after the 50 µg dose and 2.1 ng/mL after the 200 µg dose, with an individual maximum of 5.7 ng/mL. Levels were detectable at 24 h for both doses. Salmeterol displayed enantioselective pharmacokinetics, with a mean ± SD log (S):(R) = 0.055 ± 0.025 (P < 0.0001) equivalent to (S):(R) of 1.13. In conclusion, rac-salmeterol by inhalation exhibits modest enantioselectivity in urine following single dose administration and can be detected following a single 50 µg dose for up to 24 h after inhalation. The present findings are of relevance if a urine threshold limit is to be introduced for salmeterol on the list of prohibited substances. The application of an enantiomer ratio analysis may offer improved discriminatory detection capability for doping control analysis applications.

  13. 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. The 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. In conclusion, this approach can quickly estimate potential dose from airborne radionuclides in wildland fire and assist decision-making to reduce firefighter exposure.

  14. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis

    PubMed Central

    Holt, Shaun; Suder, Aneta; Weatherall, Mark; Cheng, Soo; Shirtcliffe, Philippa; Beasley, Richard

    2001-01-01

    Objective To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma. Design Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone. Setting Medline, Embase, and GlaxoWellcome's internal clinical study registers. Main outcome measures FEV1, morning and evening peak expiratory flow, night awakenings, β agonist use, and major exacerbations. Results Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500 μg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 μg/day and peaked by 500 μg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit at 1000 μg/day was achieved at doses of 70-170 μg/day and 90% by 100-250 μg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses of around 500 μg/day. The odds ratio for patients remaining in a study at a dose of 200 μg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV1 for an inhaled dose of 200 μg/day against higher doses showed a difference in FEV1 of 0.13 of a standard deviation (−0.02 to 0.29). Conclusions In adolescent and adult patients with asthma, most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250 μg, and the maximum effect is achieved with a dose of around 500 μg/day. However, these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 μg/day. What is already known on this topicInhaled corticosteroids are recommended for most patients with asthma, with the dose being increased as required to obtain controlA therapeutic dose

  15. Pharmacokinetics and systemic activity of fluticasone via Diskus® and pMDI, and of budesonide via Turbuhaler®

    PubMed Central

    Thorsson, Lars; Edsbäcker, Staffan; Källén, Anders; Löfdahl, Claes-Göran

    2001-01-01

    Aims To determine the basal pharmacokinetics, lung uptake and plasma cortisol suppression for two commonly prescribed inhaled corticosteroids. Methods Twenty-one subjects (13 healthy and 8 mild asthmatic patients) received fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus® and budesonide via Turbuhaler®, 1000 µg twice daily for 7 days. Intravenous doses (200 µg) of both compounds were used as references. Plasma concentrations of fluticasone and budesonide were determined during 48 h by liquid chromatography plus tandem mass spectrometry (LC-MS-MS). Plasma concentrations of cortisol were determined by LC-MS every second hour for 24 h at baseline, and following each treatment. Results The volume of distribution was found to be larger and the elimination half-life and mean absorption time longer for fluticasone than for budesonide. The systemic availability of budesonide via Turbuhaler (39%) was significantly higher than that of fluticasone via Diskus (13%) (ratio 3.0 [2.5, 3.6] with 95% confidence interval [CI]), and via pMDI (21%) (ratio 1.8 [1.3, 2.3]). In addition, at steady state the systemic availability of fluticasone via pMDI was significantly higher than via Diskus (ratio 1.6 [1.1, 2.2]). The lung deposition of budesonide via Turbuhaler was 2.2-fold [1.7, 2.9] higher than that of fluticasone pMDI and 3.4-fold [2.8, 4.0] higher than that of fluticasone Diskus. In addition, the lung deposition of fluticasone via pMDI was 1.5-fold [1.1, 2.9] higher than that via the Diskus inhaler. Plasma cortisol (24 h) was significantly reduced vs baseline for all three treatments. The cortisol concentration vs baseline was 12% for fluticasone pMDI, which was significantly lower (ratio 0.32 [0.24, 0.42]) than that for fluticasone Diskus (39%), and for budesonide Turbuhaler (46%) (ratio 0.27 [0.21, 0.37]). The plasma cortisol concentration did not differ significantly between treatments with

  16. 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.

  17. Raman spectroscopy for the process analysis of the manufacturing of a suspension metered dose inhaler.

    PubMed

    Butz, James; de la Cruz, Luis; DiTonno, Jason; DeBoyace, Kevin; Ewing, Gary; Donovan, Brent; Medendorp, Joseph

    2011-04-05

    The purpose of this research was to demonstrate the utility of Raman spectroscopy for process analysis of a suspension metered dose inhaler manufacturing process. Chemometric models were constructed for the quantification of ethanol and active pharmaceutical ingredient such that both could be monitored in real-time during the compounding and filling operations via tank measurements and recirculation line flow-cell measurements. Different spectral preprocessing techniques were used to delineate the effects of mixing speed and temperature changes from actual concentration effects. Raman spectroscopy offers advantages in time savings and quality of information over the standard methods of analysis for respiratory formulations, such as a drug content assay via HPLC and ethanol testing via GC. The successful implementation of this work will allow formulation scientists to quantitatively assess both the formulation (e.g., the concentration of active pharmaceutical ingredient (API) and ethanol), as well as the manufacturing process (e.g., determination of mixing endpoints) in real-time.

  18. Novel cosuspension metered-dose inhalers for the combination therapy of chronic obstructive pulmonary disease and asthma.

    PubMed

    Lechuga-Ballesteros, David; Noga, Brian; Vehring, Reinhard; Cummings, R Harris; Dwivedi, Sarvajna K

    2011-10-01

    Pressurized metered dose inhaler is the most common inhaled dosage form, ideally suited for delivering the highly potent compounds that medicinal chemists typically discover for respiratory therapeutic targets. The clinical benefit of combination therapy for asthma and chronic obstructive pulmonary disease has been well established, and many of the new discovery candidates are likely to be studied in the clinic as combination drugs even at early stages of development. We present a novel pressurized metered dose inhaler formulation approach to enable consistent aerosol performance of a respiratory therapeutic whether it is emitted from a single-, double- or triple-therapy product. This should enable rapid nonclinical and clinical assessment whether alone or in combination with other drugs, without the challenge of in vitro performance dissimilarity across product types.

  19. Design optimization of a novel pMDI actuator for systemic drug delivery.

    PubMed

    Kakade, Prashant P; Versteeg, Henk K; Hargrave, Graham K; Genova, Perry; Williams Iii, Robert C; Deaton, Daniel

    2007-01-01

    Pressurized metered dose inhalers (pMDIs) are the most widely prescribed and economical respiratory drug delivery systems. Conventional pMDI actuators-those based on "two-orifice-and-sump" designs-produce an aerosol with a reasonable respirable fraction, but with high aerosol velocity. The latter is responsible for high oropharyngeal deposition, and consequently low drug delivery efficiency. Kos' pMDI technology is based on a proprietary vortex nozzle actuator (VNA), an innovative actuator configuration that seeks to reduce aerosol plume velocity, thereby promoting deep lung deposition. Using VNA development as a case study, this paper presents a systematic design optimization process to improve the actuator performance through use of advanced optical characterization tools. The optimization effort mainly relied on laser-based optical diagnostics to provide an improved understanding of the fundamentals of aerosol formation and interplay of various geometrical factors. The performance of the optimized VNA design thus evolved was characterized using phase Doppler anemometry and cascade impaction. The aerosol velocities for both standard and optimized VNA designs were found to be comparable, with both notably less than conventional actuators. The optimized VNA design also significantly reduces drug deposition in the actuator as well as USP throat adapter, which in turn, leads to a significantly higher fine particle fraction than the standard design (78 +/- 3% vs. 63 +/- 2% on an ex valve basis). This improved drug delivery efficiency makes VNA technology a practical proposition as a systemic drug delivery platform. Thus, this paper demonstrates how advanced optical diagnostic and characterization tools can be used in the development of high efficiency aerosol drug delivery devices.

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

    PubMed

    Hodder, Richard; Price, David

    2009-01-01

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

  1. Inhaler spacer devices to treat asthma in children.

    PubMed

    Watson, Paul

    Drawing on literature searches and professional experience, this article discusses the treatment of asthma with pressurised metered dose inhalers (pMDIs). It demonstrates the need for pMDIs, and presents the health and cost benefits of using a pMDI through a spacer device. Through the review and evaluation of studies, it demonstrates the importance of correct asthma management and the use of spacers. Although there are many types of spacer, and patients often have less than optimal technique, there is evidence to support the overall benefits of use against non-use.

  2. Inhalation dose due to radon, thoron, and progenies in dwellings of a hill station.

    PubMed

    Sivakumar, R

    2017-02-01

    The general public spends a major portion of their time in an indoor environment and hence receives a considerable amount of radiation. Knowledge about indoor radiation is important in order to arrive at the actual effective dose received by residents. The indoor radon, thoron, and progeny concentrations observed in the present study were found to vary with seasons of a given year. The highest and lowest indoor average radon, thoron, and progeny levels were observed during winter and summer seasons, respectively. The concentrations of indoor radon, thoron, and progenies were found to vary with the type of houses. The highest (222)Rn, (220)Rn, and progeny concentrations were observed in mud houses and the lowest values were recorded in wooden houses. The indoor (222)Rn concentration correlated well with concentration of its grandparent (238)U in underlying soil with a correlation coefficient of 0.87. The correlation between indoor (220)Rn and (232)Th in the underlying soil was found to be 0.64. The estimated effective doses received by the general public in the present study due to indoor radon and thoron were 1.49 ± 0.49 and 1.30 ± 0.53 mSv/year, respectively. The annual effective doses due to radon and thoron progenies were estimated as 0.76 ± 0.27 and 0.47 ± 0.23 mSv/year, respectively. The contributions from (222)Rn, (220)Rn, and corresponding progenies to the annual effective doses received were 37, 32, 19, and 12%, respectively. The general public living in the study area receives an inhalation dose of 4.02 mSv/year due to indoor radon, thoron, and progenies, which were found to be less than the action limit of ICRP 2009.

  3. 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...

  4. 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...

  5. Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting β-Agonist for Step-Up Therapy in Asthma.

    PubMed

    Israel, Elliot; Roche, Nicolas; Martin, Richard J; Colice, Gene; Dorinsky, Paul M; Postma, Dirkje S; Guilbert, Theresa W; van Aalderen, Willem M C; Grigg, Jonathan; Hillyer, Elizabeth V; Burden, Anne; von Ziegenweidt, Julie; Thomas, Victoria; Price, David B

    2015-06-01

    Guidelines advocate adding long-acting β-agonist (LABA) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy. However, less than 5% of patients with asthma qualify for the randomized controlled trials on which guidelines are based. Thus, real-world data are needed to complement the results of randomized trials with narrow entry criteria. To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA. We performed a historical matched cohort study using large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid versus added LABA for patients 12-80 years old. As outcomes, we examined a composite of asthma control and rates of severe exacerbations. The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA. The adjusted odds ratios (95% confidence interval) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809 per cohort). The adjusted rate ratios (95% confidence interval) for severe exacerbations, compared with inhaled corticosteroid/LABA combination inhaler, were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not affected by smoking status. When applied to a broad primary care population, antiinflammatory therapy using increased doses of small- or standard size-particle inhaled corticosteroid is as effective as adding LABA, as measured by outcomes important to both patients and providers. Real-world populations and outcomes need to be taken into

  6. Application of co-grinding to formulate a model pMDI suspension.

    PubMed

    Williams, R O; Repka, M A; Barron, M K

    1999-09-01

    The objective of this study was to investigate the effect of co-grinding the model drug, triamcinolone acetonide (TAA), with a polymeric surfactant on the in vitro performance of a model pMDI suspension system. The physicochemical properties of TAA after co-grinding with the surfactant, Pluronic F77, were determined by laser light diffraction, helium pycnometry and equilibrium solubility measurements. TAA-surfactant interaction was investigated by differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). The suspension characteristics of pMDI formulations prepared with co-ground TAA and surfactant were investigated by determining their in situ sedimentation, rheological profiles and vapor pressure. The performance characteristics of the pMDI formulations were determined by cascade impaction and dose delivery through-the-valve (DDV) measurements. It was found that the presence of Pluronic F77 decreased the solubility of TAA in the propellant medium. Co-grinding TAA particles with Pluronic F77 influenced the particle size distribution, sedimentation and flocculation characteristics of the pMDI suspension formulation. The addition of Pluronic F77 decreased the viscosity of the pMDI formulation. Formulating the suspension pMDI system with co-ground TAA and Pluronic F77 decreased the mass median aerodynamic diameter (MMAD) of the emitted aerosol and increased the percent respirable fraction (%RF). The co-ground TAA and Pluronic F77 pMDI suspension formulation exhibited greater physical stability which was due to the influence of the co-grinding technique on the physicochemical properties of the TAA particle surface and the propellant dispersion medium. The changes induced by co-grinding with Pluronic F77 improved the performance characteristics of a pMDI suspension formulation by stabilizing the suspension and influencing the flocculation characteristics. Co-grinding is a process which may be useful when developing new pMDI systems containing

  7. Inhaler Technique in Children With Asthma: A Systematic Review.

    PubMed

    Gillette, Chris; Rockich-Winston, Nicole; Kuhn, JoBeth A; Flesher, Susan; Shepherd, Meagan

    2016-01-01

    Pediatric asthma is an important public health problem worldwide. The primary methods of medication delivery are inhalation devices. This systematic review examined: 1) what is the prevalence of correct inhaler technique among children with asthma, 2) are educational interventions associated with improved rates of correct inhalation technique, and 3) is improved inhaler technique associated with improved asthma outcomes? We included experimental and observational studies through searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL Complete, and clinicaltrials.gov. Studies were eligible for this review if at least 1 outcome measure of the study included and reported results of child/adolescent inhaler technique. The following information was extracted from each included study: study design (experimental vs observational), and outcomes data. The Downs and Black checklist was used to appraise study quality. Twenty-eight studies were eligible for inclusion. We found that inhaler technique is generally very poor among children, but is better when children use their metered-dose inhalers (MDIs) with spacers. Technique in using turbuhalers and diskus inhalers is better than in MDI, but still poor. Counseling children on correct inhaler technique was associated with improved technique among children in multiple studies. We examined articles published in English. Inhaler technique in children is generally poor. Physicians and other members of the health care team should instruct children and their caregivers on the proper use of their inhalation devices at every opportunity and correct mistakes when made to ensure effective medication delivery. This systematic review was registered under the Centre for Reviews and Dissemination, PROSPERO CRD42015025070 (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015025070). Copyright © 2016. Published by Elsevier Inc.

  8. Dose estimate of inhaled hafnium tritide using the ICRP 66 lung model.

    PubMed

    Cheng, Yung-Sung; Zhou, Yue; Wang, Yang-Sheng; Inkret, William C; Wermer, Joseph R

    2002-06-01

    Metal tritide is widely used for research, purification, compression, and storage of tritium. The current understanding of metal tritide and its radiation dosimetry for internal exposure is limited, and ICRP publications do not provide the tritium dosimetry for hafnium tritide. The current radiation protection guidelines for metal tritide particles (including hafnium tritide) are based on the assumption that their biological behavior is similar to tritiated water, which is completely absorbed by the body. However, the solubility of metal tritide particles depends on the chemical form of the material. The biological half-live of hafnium tritide particles and the dosimetry of an inhalation exposure to those particles could be quite different from tritiated water. This paper describes experiments on the dissolution rate of hafnium tritide particles in a simulated lung fluid. The results showed that less than 1% of the tritium was dissolved in the simulated lung fluid for hafnium tritide particles after 215 d. The short-term and long-term dissolution half times were 46 and 4.28 x 10(5) d, respectively. This indicates that hafnium tritide is an extremely insoluble material. Self-absorption of beta rays in the hafnium tritide particles was estimated by a numerical method. The dose coefficients were calculated as a function of particle size using in vitro solubility data and a calculated self-absorption factor. The dose coefficient decreased with aerodynamic diameters in the range of 0.25 to 10 microm, mainly because the self-absorption factor decreased with increasing particle size. For a particle 1 microm in aerodynamic diameter, the dose coefficient of a hafnium tritide particle was about 10 times higher than that of tritiated water but was about 1.4 times lower than that calculated by ICRP Publication 71 for Type S tritiated particles. The ICRP estimate did not include a self-absorption factor and thus might have overestimated the dose. This finding has significant

  9. Inhaler technique in Turkish people with poor English: a case of information discrimination?

    PubMed

    Goodyer, Larry; Savage, Imogen; Dikmen, Zeynep

    2006-04-01

    (a) To compare metered dose inhaler (MDI) technique in users with poor English and fluent English, (b) to evaluate two interventions: a translated patient information leaflet (PIL) plus support from an translator (PIL + verbal) and a multimedia touch screen system (MTS) using video clips and own-language instruction. (a) Inhaler technique was videotaped and key steps rated blind for 105 fluent English-speakers (FE) and 69 Turkish-speakers with poor English (EP). (b) The EP group was randomised to receive information by MTS (n = 34) or PIL + verbal (n = 35). Inhaler technique was videotaped before and after information. (a) Global inhaler technique; (b) breathing-in time; (c) co-ordination of inspiration and inhaler actuation. Global technique, co-ordination and breath-holding were all significantly worse in MDI users with poor English. Only 17% of that group had adequate technique compared to over half (62%) of FE. The EP group were significantly less likely than the FE group to report ever seeing the practice nurse about their asthma. After information, global technique was rated as improved in 50% of the MTS group compared to 28% of those given a translated PIL. A further six people (17%) in the PIL group improved after subsequent verbal advice in their own language. Both information methods significantly increased inhaler shaking and mouthpiece checking, but co-ordination only improved in a small number of people. The study suggests that Turkish-speaking MDI users with poor English may be disadvantaged in terms of access to medicines information in the UK. The acceptability of pharmacy-based support services for this, and other specific language groups should be explored. Multimedia offers an alternative to a translator for brief explanations, particularly for first-time users, but improving poor co-ordination requires individualised "hands on" teaching from health professionals.

  10. Assessment of the factors affecting the failure to use inhaler devices before and after training.

    PubMed

    Aydemir, Yusuf

    2015-04-01

    Inhaler devices used for the treatment of chronic respiratory diseases are frequently incorrectly used by the patients. The effects of training on the correct use of these devices are unquestionable. However, despite the training provided on the correct technique of using the inhaler device, some patients still continue using the device incorrectly. The aims of the present study are to determine the rate of incorrect use of the inhaler devices, assess the parameters that affect the incorrect use, demonstrate the contribution of training, and determine the characteristics of the patients who use the devices incorrectly despite training. 342 consecutive patients were included in the study. The patients' ability to use the devices correctly was scored before and after face-to-face trainings. The parameters affecting incorrect use, the impact of training, and characteristics of the patients who continued the incorrect usage after training were evaluated. The rate of correct usage was 58.9% for dry powder inhalers (DPI) and 31.1% for pressurized metered dose inhalers (pMDI) before the training. The parameters affecting correct usage were educational status, gender, living in rural areas, duration of disease, and being diagnosed and followed-up by a chest diseases specialist. The rate of correct usage increased to 92.6% for DPI and 45.2% for pMDI after the training. The factors affecting continued incorrect usage after standard training were old age and the type of the pMDI device. The technique for using the inhaler device should be described to the patients in a face-to-face session by the prescribing physician. Device selection should be done on a "trial" basis and it should be considered that particularly older patients and those using pMDIs continue using the devices incorrectly despite training; hence, alternative treatment options should be reviewed for these patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility.

    PubMed

    Kang, Gi Soo; Gillespie, Patricia A; Gunnison, Albert; Rengifo, Hernan; Koberstein, Jeffrey; Chen, Lung-Chi

    2011-02-01

    In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4?h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and nano-NH appeared to have stronger inflammogenic potential than nano-NS even when lung Ni burden taken into consideration. This suggests that the toxicity of nano-NH is not driven solely by released Ni ions from deposited nano-NH particles. However, it is unlikely that the greater toxic potential of nano-NH is attributable to a generic stress response from any nanoparticle exposure, since nano-C and nano-Ti did not elicit toxic responses similar to those of nano-NH. These results indicate that the observed pulmonary toxicity by inhaled nano-NH were chemical-specific and deposited dose and solubility are key factors to understand toxicity induced by nano-NH.

  12. 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.

  13. Ventilation heterogeneity predicts asthma control in adults following inhaled corticosteroid dose titration.

    PubMed

    Farah, Claude S; King, Gregory G; Brown, Nathan J; Peters, Matthew J; Berend, Norbert; Salome, Cheryl M

    2012-07-01

    Asthma guidelines recommend inhaled corticosteroid (ICS) dose titration for patients on the basis of an assessment of current asthma control. However, the physiological determinants of asthma symptom control are poorly understood and spirometry is a poor predictor of symptomatic response. To determine the role of small airway measurements in predicting the symptom response following ICS dose titration. Adult asthmatic patients had the Asthma Control Questionnaire (ACQ) scores and lung function measured at baseline and after 8 weeks. Tests included spirometry, plethysmography, sputum cell count, exhaled nitric oxide, airway hyperresponsiveness to mannitol, respiratory system mechanics using the forced oscillation technique, and ventilation heterogeneity using the multiple breath nitrogen washout. The parameters ventilation heterogeneity in convection-dependent airways and ventilation heterogeneity in diffusion-dependent airways were derived as measures of ventilation heterogeneity in the small airways. The dose of ICS was doubled if the ACQ score was greater than or equal to 1.5 (uptitration) and quartered if the ACQ score was less than 1.5 (downtitration). The relationships between baseline physiological parameters and the change in the symptom-only 5-item ACQ (deltaACQ-5) were examined by using Spearman correlations, forward stepwise linear regressions, and receiver operator curve analyses. ICS dose uptitration (n= 20) improved ACQ-5 scores (1.76 to 1.16; P= .04). Baseline fraction of exhaled nitric oxide (r= -0.55; P= .01) and ventilation heterogeneity in convection-dependent airways (r= -0.64; P= .002) correlated with deltaACQ-5, but ventilation heterogeneity in convection-dependent airways was the only independent predictor (r(2) = 0.34; P = 0.007). ICS dose downtitration (n= 41) worsened ACQ-5 scores (0.46 to 0.80; P< .001), with 29% of the patients having a deltaACQ-5 of greater than 0.5. Only baseline ventilation heterogeneity in diffusion-dependent airways

  14. Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane [correction to piphenylmethane] diisocyanate (MDI).

    PubMed

    Vandenplas, O; Malo, J L; Dugas, M; Cartier, A; Desjardins, A; Lévesque, J; Shaughnessy, M A; Grammer, L C

    1993-02-01

    Isocyanates are well documented as a cause of occupational asthma. A hypersensitivity pneumonitis type of reaction has also been reported but only in a few isolated cases. We investigated nine subjects who complained of respiratory and general symptoms related to workplace exposure. All the subjects had worked in a plant where a resin based on diphenylmethane diisocyanate (MDI) is used in the manufacture of woodchip boards. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. In eight subjects, exposure to subirritant amounts of MDI induced a pattern of reaction consistent with hypersensitivity pneumonitis, i.e., significant falls in both FEV1 and FVC associated with a rise in body temperature (> 38 degrees C) and an increase in blood neutrophils (> +2,500/mm3). Bronchoalveolar lavage, performed in two subjects 24 h after the end of challenge exposure, revealed an increase in lymphocytes and neutrophils. Specific immunoglobulin G (IgG) and IgE antibodies to MDI human serum albumin (HSA) conjugates were present in all subjects. We conclude that the MDI resin caused an hypersensitivity pneumonitis type of reaction in at least eight (4.7%) of the 167 potentially exposed workers employed in the plant. These findings indicate that in some workplaces, a hypersensitivity pneumonitis type of reaction may be a more frequent consequence of isocyanate exposure than is usually thought.

  15. Methylene Diphenyl Diisocyanate (MDI) And Related Compounds

    EPA Pesticide Factsheets

    This document addresses the use of methylene diphenyl diisocyanate (MDI) and related compounds (See Appendix 1) in products that may result in consumer and general population exposures, particularly in or around buildings, including homes and schools.

  16. Methylene Diphenyl Diisocyanate (MDI) And Related Compounds

    EPA Pesticide Factsheets

    This document addresses the use of methylene diphenyl diisocyanate (MDI) and related compounds (See Appendix 1) in products that may result in consumer and general population exposures, particularly in or around buildings, including homes and schools.

  17. Model Calculations of Regional Deposition and Disposition for Single Doses of Inhaled Liposomal and Dry Powder Ciprofloxacin.

    PubMed

    Martin, Andrew R; Finlay, Warren H

    2017-07-14

    Model predictions of regional deposition in the respiratory tract are useful in assessing factors that influence the effectiveness of aerosol delivery. Regional deposition models have previously been coupled with models of mucous production and clearance to estimate initial concentrations of drug deposited in the airway surface liquid (ASL) lining tracheobronchial airways. Established models of regional deposition and ASL volumes were used to provide input to a new model evaluating the disposition of drug resulting from dissolution or release, absorption, and mucociliary clearance. Additional modeling of oral absorption, distribution, and elimination allowed prediction of systemic exposure. Herein, predicted ASL and plasma concentrations of free (dissolved or unencapsulated) ciprofloxacin over time are reported for a healthy, adult lung model following inhalation of single doses of nebulized liposomal (6 mL of liposomal ciprofloxacin for inhalation, 50 mg/mL, or 6 mL of Pulmaquin, 210 mg; Aradigm) and dry powder (32.5 and 65 mg doses; Bayer) formulations. Over a range of mucous production rates and tracheal clearance velocities, peak ASL concentrations of free ciprofloxacin were consistently greater for Pulmaquin than for other formulations investigated, owing to the presence of free drug in the nebulized Pulmaquin formulation. The time that ASL concentrations of free drug remained above the minimum inhibitory concentration for Pseudomonas aeruginosa was similar for all four formulations. Predicted plasma ciprofloxacin concentration profiles were in good agreement with available data from Phase I trials in healthy volunteers. Predictions of ASL drug concentrations over time are valuable in elucidating the roles of deposition, drug release or dissolution, and disposition on the effectiveness of inhaled aerosol therapies. For inhaled ciprofloxacin, the present results predict similar ASL concentrations of free drug over time following single doses of

  18. Salbutamol via metered-dose inhaler with spacer versus nebulization for acute treatment of pediatric asthma in the emergency department.

    PubMed

    Benito-Fernández, Javier; González-Balenciaga, María; Capapé-Zache, Susana; Vázquez-Ronco, Miguel A; Mintegi-Raso, Santiago

    2004-10-01

    To assess the effectiveness of salbutamol delivered via a metered-dose inhaler with spacer versus a nebulizer for acute asthma treatment in the pediatric emergency department. All consecutive children younger than 14 years old who required treatment of acute asthma exacerbation in the emergency department during May 2002 (prospective cohort, n = 321) and May 2001(retrospective cohort, n = 259) were included. Inhaled salbutamol was administered by metered-dose inhaler with a spacer (and a face mask in children younger than 2 years old) in the prospective cohort and by nebulizer in the retrospective cohort. There were no significant differences between the two cohorts in the mean (+/-SD) age (44.50 +/- 38.64 vs. 48.37 +/- 43.55 months) and asthma treatment, arterial oxygen saturation (96.34 +/- 2.12% vs. 96.19 +/- 6.32%), and heart rate (123.71 +/- 23.63 vs. 129.41 +/- 34.55 beats/min) before emergency department consultation. The number of doses of inhaled bronchodilators was also similar (1.42 +/- 1.01 vs. 1.45 +/- 0.98) as well as the number of children that required a stay in the observation unit, admission to the hospital, or returned for medical care. The overall mean length of stay in the emergency department was slightly shorter in the prospective cohort (82 +/- 48 vs. 89 +/- 52 minutes). The administration of bronchodilators using a metered-dose inhaler with spacer is an effective alternative to nebulizers for the treatment of children with acute asthma exacerbations in the emergency department.

  19. 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

  20. Inhaled corticosteroid dose response using domiciliary exhaled nitric oxide in persistent asthma: the FENOtype trial.

    PubMed

    Anderson, William J; Short, Philip M; Williamson, Peter A; Lipworth, Brian J

    2012-12-01

    International guidelines advocate a standard approach to asthma management for all, despite its heterogeneity. "Personalized" treatment of inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose response to inhaled corticosteroids (ICSs) in patients with asthma with an elevated fractional exhaled nitric oxide (Feno) phenotype using domiciliary measurements. We performed a randomized, crossover trial in 21 patients with mild to moderate persistent asthma receiving ICSs with elevated Feno (>30 parts per billion [ppb]) that increased further (>10 ppb) after ICS washout. Patients were randomized to 2 weeks of either fluticasone propionate 50 μg bid (FP100) or 250 μg bid (FP500). The primary outcome was response in diurnal domiciliary Feno levels. Secondary outcomes included mannitol challenge, serum eosinophilic cationic protein (ECP), blood eosinophil count, and asthma control questionnaire. We found significant dose-related reductions of diurnal Feno compared with baseline - morning Feno: baseline = 71 ppb (95% CI, 61-83 ppb); FP100 = 34 ppb (95% CI, 29-40 ppb), P < .001; FP500 = 27 ppb (95% CI, 22-33 ppb), P < .001; and significant dose separation for morning, P < .05, and evening, P < .001. Time-series Feno displayed exponential decay: FP100 R² = 0.913, half-life = 69 h (95% CI, 50-114 h); FP500 R² = 0.966, half-life = 55 h (95% CI, 45-69 h), as well as diurnal variation. The Asthma Control Questionnaire showed significant improvements exceeding the minimal important difference (>0.5) with values in keeping with controlled asthma (<0.75) after each dose: FP100 = 0.48 (95% CI, 0.24-0.71), P = .004; FP500 = 0.37 (95% CI, 0.18-0.57), P = .001. All other secondary inflammatory related outcomes (mannitol, ECP, and eosinophils) showed significant improvements from baseline but no dose separation. There is a significant dose response of diurnal Feno to ICS in patients with asthma with an elevated Feno phenotype, which translates into well

  1. 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

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

    PubMed Central

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

    1995-01-01

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

  3. 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.

  4. [Indication and effect of inhaled DSCG for the treatment of adult asthmatics].

    PubMed

    Arai, Y

    1996-11-01

    International guidelines have recommended the early use of anti-inflammatory therapy in the treatment of asthma. Currently available anti-inflammatory agents include the corticosteroid hormones and the non-steroid drugs, nedocromil sodium (currently not available in Japan) and disodium cromoglycate (DSCG). In general, DSCG has shown clinical activity in atopic young patients with mild asthma who do not require inhaled corticosteroids as maintenance therapy. However, nebulised DSCG showed early, significant improvements in symptoms and peak expiratory flow rate in non-atopic as well as atopic asthmatics with severe asthma who require high doses of inhaled and oral corticosteroids as maintenance therapy. In adult asthmatics, it is important that the choice of mode of administration of DSCG is made according to asthma severity, such as using metered dose inhaler (MDI) for mild asthma and the nebulised formulation for more severe asthma.

  5. 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

  6. Terbutaline: level the playing field for inhaled β2-agonists by introducing a dosing and urine threshold.

    PubMed

    Jacobson, Glenn A; Hostrup, Morten

    2017-09-01

    Terbutaline, a short-acting β2-agonist similar to salbutamol, is widely used in Europe in the treatment of asthma and exercise-induced bronchoconstriction. Unlike salbutamol, terbutaline requires therapeutic use exemption (TUE) for therapeutic inhaled use in competitive sport. There is now compelling evidence that supratherapeutic use of terbutaline is performance enhancing, via oral dosing and inhalation. It is likely that the ergogenic effects of terbutaline are class specific for all β2-agonists. The World Anti-Doping Agency (WADA) has introduced dosing and urine threshold and decision limits for other common β2-agonists. This allows athletes to use these drugs for therapeutic purposes while minimising the potential for doping and administrative burden of TUEs. However, no such threshold limits currently exist for terbutaline. For terbutaline, athletes can be granted a TUE, then administer the drug via inhalation at supratherapeutic doses with impunity. The introduction of threshold dosing and urine limits for terbutaline should be a high priority, given the drug's demonstrated ergogenic effects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Periodontal disease and high doses of inhaled corticosteroids alter NTPDase activity in the blood serum of rats.

    PubMed

    Scarabelot, Vanessa L; Cavagni, Juliano; Medeiros, Liciane F; Detânico, Bernardo; Rozisky, Joanna R; de Souza, Andressa; Daudt, Luciana Dondonis; Gaio, Eduardo José; Ferreira, Maria Beatriz Cardoso; Rösing, Cassiano Kuchenbecker; Battastini, Ana Maria O; Torres, Iraci L S

    2014-08-01

    Certain drugs such as glucocorticoids may interfere with the modulation of periodontal disease. In contrast, corticosteroid treatment has been associated with a protective effect with regard to periodontal breakdown, depending on the dose, pathway, and exposure time. Considering the potential relevance of nucleotidases in coordinating the cardiovascular system and inflammation processes, the aim of this study was to investigate the nucleotidase activities in the blood serum of rats with periodontal disease exposed chronically to inhaled corticosteroids. Adult male Wistar rats (n=26) were randomly assigned to one of the following four study groups: a control group that received no intervention; a periodontal disease group that received saline solution; a 'low dose' group that received 30 μg of budesonide daily; and a corresponding 'high dose' group that received 100 μg daily over a 15-day time course. The hydrolysis of ATP, ADP, and AMP were analysed in blood serum. Periodontal disease diminished the hydrolysis of ATP and enhanced the hydrolysis of ADP. Repeated administration of either a low or high dose in the periodontal disease model of inhaled corticosteroids reversed the observed increase in ADP hydrolysis, and only the repeated administration of low doses of inhaled corticosteroids was able to reverse the decrease in the hydrolysis of ATP induced by periodontal disease. The variables investigated in this study may be involved in the pathophysiology of periodontal disease and may participate in the mechanisms that mediate the development of some of the side effects of inhaled corticosteroids. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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

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

    PubMed

    Manabe, K; Endo, A; Eckerman, K 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.

  10. Investigations into the formulation of metered dose inhalers of salmeterol xinafoate and fluticasone propionate microcrystals.

    PubMed

    Murnane, Darragh; Martin, Gary P; Marriott, Christopher

    2008-10-01

    To investigate the aerosolization and behaviour of microparticles of salmeterol xinafoate (SX) and fluticasone propionate (FP) suspended in hydrofluoroalkane (HFA) propellant. Microcrystals of SX and FP were produced from poly(ethylene glycol) by antisolvent crystallization. The suspension behaviour and aerosolization of the microcrystals when formulated as metered dose inhalers (MDIs) in HFA 134a propellant was compared with that of microparticles produced by micronization (mSX and mFP) using a glass twin stage impinger and by laser light diffraction using a pressurized cell. FP microparticles underwent non-reversible aggregation in suspension as seen by a doubling in the volume median diameter compared to the raw material. The degree of aggregation of SX particles in suspension was found to decrease as the particle size of the original particles increased. However, because the SX aggregate size was lowest for the particles with the smallest initial size (mSX), the highest fine particle fraction (FPF) of SX was obtained from a suspension of mSX. The FPFs following aerosolization of FP suspensions were similar although the FPF was lowest for particles with the largest original size. The size of the aggregates in the HFA suspensions was found to correlate directly with the FPFs determined by impaction.

  11. 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.

  12. Surface energy and interparticle forces correlations in model pMDI formulations.

    PubMed

    Traini, Daniela; Rogueda, Philippe; Young, Paul; Price, Robert

    2005-05-01

    To compare experimental measurements of particle cohesion and adhesion forces in a model propellant with theoretical measurements of the interfacial free energy of particulate interactions; with the aim of characterizing suspension stability of pressurized metered dose inhalers (pMDIs). Interparticulate forces of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate were investigated by in situ atomic force microscopy (AFM) in a model propellant 2H,3H perfluoropentane. The surface thermodynamic properties were determined by contact angle (CA) and inverse gas chromatography (IGC). Experimental data were compared with theoretical work of adhesion/cohesion using a surface component approach (SCA), taking into account both dispersive and polar contributions of the surface free energy. Results indicated that the measured forces of interaction between particles in model propellant could not be accounted for by theoretical treatment of the dispersive surface free energies via CA and IGC. A correlation between theoretical work of adhesion/cohesion and AFM measurements was observed upon the introduction of the polar interfacial interactions within the SCA model. It is suggested that the polar contributions of the surface free energy measurements of particles may play a crucial role in particle interaction within propellant-based systems. Together with the application of a SCA model, this approach may be capable of predicting suspension stability of pMDI formulations.

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

    PubMed

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

    2010-09-01

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

  14. INHALER COUNSELLING, THE REAL DEAL OR JUST FRESH AIR?

    PubMed

    Goodwin, Richard; Chander, Tiranvir; Shah, Neha; Tomlin, Steve

    2016-09-01

    To evaluate whether healthcare professionals within the local community are able to counsel paediatric patients on the essential steps required for drug delivery with multi-dose inhalers (MDI), MDIs with a spacer and turbohalers. An expert panel produced and piloted checklists for essential and good practice counselling steps. Eligible participants included healthcare professionals regularly counselling children on inhaler devices, including doctors, nurses and pharmacy team members. Participants were recruited through purposive sampling on a general paediatric ward in a major children's hospital over 2 months and local community pharmacies. Participants counselled on each technique through simulated paediatric scenarios and were assessed by a trained researcher. The audit captured 92 healthcare professionals, comprising 43 nurses, 9 doctors, 13 hospital pharmacy staff and 27 community pharmacies team members.Overall 13% (12/92) of participants counselled on all the essential criteria for an MDI inhaler. Pharmacy teams within the hospital and community saw the highest competency levels with 31% (4/13) and 30% (8/27) of staff able to discuss the essential steps respectively, no doctors or nurses were able to indentify all steps.10% (9/92) of participants were able to counsel on all essential steps for a MDI with a spacer device, with no nurse nor doctor achieving all steps. Hospital pharmacy staff were most likely to discuss all the essential steps with 6/13 staff competent and 3/27 community pharmacy team members counselled on the required steps. Commonly omitted steps included shaking the inhaler and leaving sufficient time between doses.Competency levels for turbohaler counselling were low, only 5 participants were able to counsel on the essential steps required. Commonly omitted or incorrect descriptions surrounded the priming of the device and incorrect inhalation technique. Our findings mirror those of previously published studies with an adult focused

  15. Exhaling a budesonide inhaler through the nose results in a significant reduction in dose requirement of budesonide nasal spray in patients having asthma with rhinitis.

    PubMed

    Shaikh, W A

    1999-01-01

    Budesonide, an inhaled corticosteroid is used routinely in the treatment of bronchial asthma and rhinitis. Although inhaled corticosteroids in therapeutic doses are unlikely to result in systemic side effects, there is as yet skepticism about their routine and prolonged use. The aim of this study was to determine whether budesonide inhalation through a metered dose inhaler, when exhaled through the nose could result in a reduction in the dose requirement of budesonide metered nasal spray in patients having perennial allergic asthma with rhinitis. This study was an open, parallel, comparative, crossover trial in which 49 young patients having perennial allergic asthma with rhinitis were divided into two groups and administered either a combination of budesonide metered dose inhaler with a budesonide nasal spray or a budesonide inhaler alone, which was to be exhaled through the nose. Both groups were later crossed over and weekly symptom scores and peak nasal inspiratory flow rates were monitored during each phase of the study. Finally, patients who volunteered from both groups were instructed to note the reduction in dose requirement of budesonide nasal spray while using a budesonide inhaler and exhaling it through the nose. The results of this study reveal that when a budesonide inhaler is exhaled through the nose, it results in an improvement in symptom scores and peak nasal inspiratory flow rates, which were significantly less than those obtained in the group using both a budesonide nasal spray and a metered dose inhaler. In addition, exhaling budesonide through the nose results in a 40.1% reduction in the dose requirement of a budesonide nasal spray, which is statistically significant (p < 0.001).

  16. 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.

  17. Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design

    PubMed Central

    Farkas, Dale R.; Hindle, Michael; Longest, P. Worth

    2015-01-01

    The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25–100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene (PTFE) along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2–20 mg). The inhalers were tested with spray dried excipient enhanced growth formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter (MMAD) of 1.53 µm and fine particle fractions (FPFs) less than 5 µm and 1 µm of 93% and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere. PMID:25986955

  18. Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design.

    PubMed

    Farkas, Dale R; Hindle, Michael; Longest, P Worth

    2015-11-01

    The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25-100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2-20 mg). The inhalers were tested with spray dried excipient enhanced growth (EEG) formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter of 1.53 μm and fine particle fractions <5 and 1 μm of 93 and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere.

  19. Inhaled corticosteroid therapy with nebulized beclometasone dipropionate.

    PubMed

    Nicolini, Gabriele; Cremonesi, Giovanni; Melani, Andrea S

    2010-06-01

    Inhaled corticosteroids (ICS) are the most effective anti-inflammatory agents for the management of chronic persistent asthma and are therefore recommended as first-line antiasthmatic therapy in children and adults. In various settings, the administration of ICS via nebulizer rather than hand-held inhaler (HHI) may have certain advantages, as many patients with HHI fail to use these devices properly or efficiently. In particular, young children, the elderly, the acutely ill, and those with restricted dexterity may be unable to coordinate inhalation with actuation of the device or to generate sufficient inspiratory flow to operate breath-actuated devices effectively. Compliance with nebulized therapy may also be better than that with a pressurized metered-dose inhaler (pMDI) plus spacer. Systematic reviews conclude that there is no significant difference in clinical effects between nebulizers and HHI. Performance and clinical effect of nebulization are influenced by several technical aspects such as the nebulizer-drug combination, nebulizer type, output and lung deposition. Among the currently available ICS, nebulized beclometasone dipropionate (BDP) has been in clinical use for more than 35 years, and has demonstrated marked clinical efficacy and a favorable tolerability profile in children and adults with chronic persistent asthma. The clinical efficacy of nebulized beclometasone is discussed in the present review using data from 13 published studies, which included a total of 1250 patients. Three multicenter, randomized, double-blind studies showed that nebulized BDP is as effective as BDP via pMDI plus spacer in a 2:1 dose ratio. Controlled trials involving 497 adults and children demonstrated similar clinical efficacy between nebulized BDP and either nebulized fluticasone propionate or nebulized budesonide. In all these trials, treatment-related adverse effects were generally uncommon, most were mild-to-moderate in severity, and most were associated with the

  20. 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...

  1. 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...

  2. A Dose-Responsive Model of Smoke Inhalation Injury. Severity-Related Alteration in Cardiopulmonary Function

    DTIC Science & Technology

    1987-07-01

    products (methane, 3 ~ethylene, propylene, and acetaldehyde ), but no cyanide-. The experimental sheep were individually exposed to 2 AY 3, 6, 9, 12...inhalation injuries. J count for some of the reported differences in lung water Trauma 1971; 11:109-117. measured in burn patients. We showed in this...9, Walker HL, McLeod CG Jr, McManus WF. Experimental inha- lation injury in the goat, J Trauma 1981; 21:962-964.useful to grade smoke inhalation as

  3. [Metered-dose inhalers with home-made spacers versus nebulizers to treat moderate wheezing attacks in children].

    PubMed

    Vilarinho, Liana Consuelo Santana; Cardeal Mendes, Carlos Maurício; de Freitas Souza, Leda Solano

    2003-01-01

    To compare the effectiveness of salbutamol administration by metered-dose inhaler with a home-made spacer versus jet nebulizer in children with moderate wheezing attacks. A randomized, single-blinded trial was performed with a convenience sample of children presenting wheezing. The children were enrolled in an emergency room and randomly assigned to one of two treatment groups: home-made spacer group or nebulizer group. Clinical scores and oxygen saturation were recorded at baseline and 15 minutes after salbutamol administration. Treatment with salbutamol (100 microg/3 kg in the spacer group, and 250 microg/3 kg in the nebulizer group) was repeated at 20-minute intervals, until the child was considered to have improved significantly, with no need of any further dose, or until three doses were delivered. Treatment cost, time spent to prepare and deliver the drug, and level of parental satisfaction with the treatment were recorded. Fifty-four children with age between 22 days and 11.7 years were enrolled--27 in each group. Baseline and demographic characteristics were similar for both groups. The spacer was as effective as the nebulizer in terms of clinical score and oxygen saturation. The different doses (100 microg/3 kg with the spacer, and 250 microg/3 kg with the nebulizer) were shown to be clinically equivalent. Treatment cost was significantly lower in the spacer group, as was the time to prepare and deliver the drug. Parental satisfaction was similar for both inhaler devices. The home-made spacer with a metered-dose inhaler is a cost-effective alternative to a jet nebulizer in the delivery of salbutamol to children with moderate wheezing attacks.

  4. Review of therapeutically equivalent alternatives to short acting β2 adrenoceptor agonists delivered via chlorofluorocarbon-containing inhalers

    PubMed Central

    Hughes, D; Woodcock, A; Walley, T

    1999-01-01

    BACKGROUND—To study the transition from metered dose inhalers using chlorofluorocarbons as propellants (CFC-MDIs) to non-CFC containing devices, a systematic review was conducted of clinical trials which compared the delivery of salbutamol and terbutaline via CFC-MDIs and non-CFC devices.
METHODS—Papers were selected by searching electronic databases (Medline, Cochrane, and BIDS) and further information and studies were sought from pharmaceutical companies. The studies were assessed for their methodological quality.
RESULTS—Fifty three relevant trials were identified. Most were scientifically flawed in terms of study design, comparison of inappropriate doses, and insufficient power for the determination of therapeutic equivalence. Differences between inhaler devices were categorised according to efficacy and potency. Most trials claimed to show therapeutic equivalence, usually for the same doses from the different devices. Two commercially available salbutamol metered dose inhalers using a novel hydrofluorocarbon HFC-134a as propellant were equally as potent and efficacious as conventional CFC-MDIs, as were the Rotahaler and Clickhaler dry powder inhalers (DPIs). Evidence suggests that a dose of 200 µg salbutamol via CFC-MDI may be substituted with 200 µg and 400 µg of salbutamol via Accuhaler and Diskhaler DPIs, respectively. Terbutaline delivered via a Turbohaler DPI is equally as potent and efficacious as terbutaline delivered via a conventional CFC-MDI.
CONCLUSIONS—When substituting non-CFC containing inhalers for CFC-MDIs, attention must be given to differences in inhaler characteristics which may result in variations in pulmonary function.

 PMID:10567628

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

    PubMed

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

    2006-01-01

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

  6. Identification of the appropriate dose metric for pulmonary inflammation of silver nanoparticles in an inhalation toxicity study.

    PubMed

    Braakhuis, Hedwig M; Cassee, Flemming R; Fokkens, Paul H B; de la Fonteyne, Liset J J; Oomen, Agnes G; Krystek, Petra; de Jong, Wim H; van Loveren, Henk; Park, Margriet V D Z

    2016-01-01

    A number of studies have shown that induction of pulmonary toxicity by nanoparticles of the same chemical composition depends on particle size, which is likely in part due to differences in lung deposition. Particle size mostly determines whether nanoparticles reach the alveoli, and where they might induce toxicity. For the risk assessment of nanomaterials, there is need for a suitable dose metric that accounts for differences in effects between different sized nanoparticles of the same chemical composition. The aim of the present study is to determine the most suitable dose metric to describe the effects of silver nanoparticles after short-term inhalation. Rats were exposed to different concentrations (ranging from 41 to 1105 µg silver/m(3) air) of 18, 34, 60 and 160 nm silver particles for four consecutive days and sacrificed at 24 h and 7 days after exposure. We observed a concentration-dependent increase in pulmonary toxicity parameters like cell counts and pro-inflammatory cytokines in the bronchoalveolar lavage fluid. All results were analysed using the measured exposure concentrations in air, the measured internal dose in the lung and the estimated alveolar dose. In addition, we analysed the results based on mass, particle number and particle surface area. Our study indicates that using the particle surface area as a dose metric in the alveoli, the dose-response effects of the different silver particle sizes overlap for most pulmonary toxicity parameters. We conclude that the alveolar dose expressed as particle surface area is the most suitable dose metric to describe the toxicity of silver nanoparticles after inhalation.

  7. [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.

  8. Evaluation of workers' exposure to methylene diphenyl diisocyanate (MDI) in an automobile manufacturing company, Iran.

    PubMed

    Kakooei, Hossein; Shahtaheri, Seyed Jamaleddin; Karbasi, Hossein-Ali

    2006-01-01

    Evaluation of personal inhalation exposure to methylene diphenyl diisocyanate (MDI) among 39 employees, working in the window fixation and window glue processes in an automobile manufacturing company was performed. This study was conducted for both case and control groups. After sampling and sample preparation processes, MDI was determined with a UV-VIS spectrophotometer at 590 nm; the lung function was assessed with a digital spirometer, too. The average concentration of MDI in the window fixation, and window glue workplaces were 34.53 and 27.37 micro g/m3, respectively, which was lower than the threshold limit value (TLV) recommended by the American Conference of Governmental Industrial Hygienists (ACGIH) (51 micro g/m3). Respiratory symptoms in the exposed group were significantly different compared to the unexposed group (p < .05). Lung capacities in the case group were lower than in the control group (p < .05). Therefore, MDI can be easily measured making it possible to evaluate the adverse effects caused by occupational exposure.

  9. Extra-fine particle inhaled corticosteroids, pharma-cokinetics and systemic activity in children with asthma.

    PubMed

    Wolthers, Ole D

    2016-02-01

    During recent years, extra-fine particle inhaled corticosteroids with a median aerodynamic diameter ≤2 μm have been introduced in the treatment of asthma. The aim of this paper was to review pharmacokinetics and systemic activity of extra-fine particle hydroalkane pressurized metered dose inhaled (pMDI) ciclesonide and beclomethasone dipropionate in children. A literature review was performed. Systemic bioavailability of oral and pulmonary deposition of extra-fine ciclesonide and beclomethasone dipropionate was 52% and 82%, the half-life in serum 3.2 and 1.5 h and first-pass hepatic metabolism >99% and 60%, respectively. Secondary analyses of urine cortisol/creatinine excretion found no effects of ciclesonide pMDI between 40 and 320 μg/day or of beclomethasone dipropionate pMDI between 80 and 400 μg/day. Ciclesonide pMDI 40, 80 and 160 μg/day caused no effects on short-term lower leg growth rate as assessed by knemometry. Ciclesonide 320 μg/day was associated with a numerically short-term growth suppression equivalent to 30% which was similar to 25% and 36% suppression caused by beclomethasone dipropionate HFA and CFC 200 μg/day, respectively. Consistent with the differences in key pharmacokinetic features, beclomethasone dipropionate is associated with a systemic activity detected by knemometry at a lower dose than ciclesonide. Whether that correlates with a clinically important difference remains to be explored. Assessments of systemic activity of beclomethasone dipropionate <200 μg/day and of ciclesonide >180 μg/day as well as head-to-head comparisons are warranted. Preferably, such studies should apply the sensitive method of knemometry.

  10. 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...

  11. 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...

  12. Low incidence of paradoxical bronchoconstriction in asthma and COPD patients during chronic use of Respimat soft mist inhaler.

    PubMed

    Hodder, Rick; Pavia, Demetri; Dewberry, Helen; Alexander, Karen; Iacono, Philippe; Ponitz, Hans; Beck, Ekkehard

    2005-09-01

    Respimat Soft Mist Inhaler (SMI) is a new-generation inhaler that offers improved lung deposition compared with chlorofluorocarbon metered dose inhalers (CFC-MDIs). Bronchodilators administered via Respimat SMI are preserved and stabilised with low concentrations of benzalkonium chloride and ethylene diamine tetra-acetic acid, both of which have been reported to cause dose-related paradoxical bronchoconstriction. The aim of this analysis was to compare the incidence of paradoxical bronchoconstriction after chronic use of bronchodilators via Respimat SMI and CFC-MDI. Data from three clinical trials, in which patients with asthma or chronic obstructive pulmonary disease (COPD) received ipratropium bromide alone or in combination with fenoterol hydrobromide, or placebo via Respimat SMI or CFC-MDI for 12 weeks, were included in the analysis. In order to evaluate the risk of paradoxical bronchoconstriction, we identified four respiratory events that might have occurred within 30 min of inhalation on four test days; these were: 'bronchospasm', 'other respiratory adverse events', 'rescue medication use' and 'asymptomatic drop in FEV(1) 15% from baseline'. In total, 631 asthma and 1538 COPD patients participated in the three studies. No occurrences of bronchospasm were reported with Respimat SMI on any test day. Overall, the incidence of respiratory events possibly indicative of paradoxical bronchoconstriction was low and similar for both devices. There was no increase in the incidence of events during 12 weeks' treatment. Delivery of bronchodilators by Respimat SMI is safe with regard to paradoxical bronchoconstriction during chronic use in patients with asthma or COPD.

  13. Acceleration Effects in MDI Magnetogram Data

    NASA Astrophysics Data System (ADS)

    Norton, A.; Settele, A.

    2003-06-01

    Acceleration effects are found in the Michelson Doppler Imager (MDI) magnetogram data because changes in the line profiles during the 30-s measurement are introduced by underlying p-mode velocity variations. This imparts an oscillatory component to the magnetic flux signal. Simulated profiles using Maltby M and Harvard Smithsonian Reference Atmospheres (HSRA) are shifted in accordance with a given velocity amplitude and period and the MDI algorithm for data measurement is applied. The simulated oscillatory component to the magnetic flux density always has a phase difference with respect to the underlying velocity of -90°. The maximum introduced RMS amplitude is a function of velocity amplitude and field strength, but realistic errors are on the order of 5/2000 G, or 0.25% of field strength. Comparison of simulations with observations shows RMS amplitudes of MDI flux density are much greater than predicted by this effect. A 2-component HSRA model, tested to determine if stronger fields with smaller fill factors could fit the data, still can not reproduce the observations. It is concluded that oscillatory amplitudes of magnetic flux density measured with MDI are not due to acceleration effects, although the effect could contribute up to 25% of the measured amplitude. Attempts to remove acceleration effects from the magnetic flux signal are not successful. Also, we confirm that velocities measured in linearly polarized light in the vicinity of a strong magnetic field contain larger errors than velocities measured in circularly polarized light (Yang and Norton, 2001).

  14. Development of the Muscle Dysmorphia Inventory (MDI).

    PubMed

    Rhea, D J; Lantz, C D; Cornelius, A E

    2004-12-01

    The development of the 6-factor, 27-item Muscle Dysmorphia Inventory (MDI) was based on Lantz et al. proposed model of characteristics associated with Muscle Dysmorphia. quantitative procedures including item-to-total correlations, exploratory and confirmatory factor analyses, and structure equation modeling confirmed the construct validity of the scale. Convergent validity was also tested. bodybuilding and powerlifting competition venues, weight training facilities, and university athletic venues. the 1(st) study consisted of 77 experienced male free weight lifters. The 2(nd) study consisted of 156 male non-competitive bodybuilders and weight lifters and 168 elite level powerlifters and bodybuilders. The 3(rd) study consisted of 151 male and female bodybuilders and weight lifters. each participant completed demographic information, the MDI, Drive for Thinness subscale of the Eating Disorder Inventory, and the Training Dependency subscale of the Bodybuilding Dependence Scale. Reliability estimates (Cronbach's a) ranged from 0.72 to 0.94. Factor loadings in all 3 studies supported the 6-factor structure (size/symmetry, supplement use, exercise dependence, pharmacological use, dietary behavior, and physique protection). Much of the scale validation was focused on construct validity, however, correlations with the MDI's subscales and the Training Dependency subscale of the Bodybuilding Dependence Scale and the Drive for Thinness subscale of the Eating Disorder Inventory provided evidence of convergent validity also. From these preliminary results, the MDI appears to contribute to the identification of a newly formed disorder by offering a multi-dimensional measure of factors related to Muscle Dysmorphia.

  15. Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler(®) 150 and 300 μg.

    PubMed

    Abadelah, Mohamad; Chrystyn, Henry; Bagherisadeghi, Golshan; Abdalla, Gaballa; Larhrib, Hassan

    2017-07-10

    Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

  16. Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles.

    PubMed

    Sayes, Christie M; Reed, Kenneth L; Glover, Kyle P; Swain, Keith A; Ostraat, Michele L; Donner, E Maria; Warheit, David B

    2010-03-01

    Inhalation toxicity and exposure assessment studies for nonfibrous particulates have traditionally been conducted using particle mass measurements as the preferred dose metric (i.e., mg or microg/m(3)). However, currently there is a debate regarding the appropriate dose metric for nanoparticle exposure assessment studies in the workplace. The objectives of this study were to characterize aerosol exposures and toxicity in rats of freshly generated amorphous silica (AS) nanoparticles using particle number dose metrics (3.7 x 10(7) or 1.8 x 10(8) particles/cm(3)) for 1- or 3-day exposures. In addition, the role of particle size (d(50) = 37 or 83 nm) on pulmonary toxicity and genotoxicity endpoints was assessed at several postexposure time points. A nanoparticle reactor capable of producing, de novo synthesized, aerosolized amorphous silica nanoparticles for inhalation toxicity studies was developed for this study. SiO(2) aerosol nanoparticle synthesis occurred via thermal decomposition of tetraethylorthosilicate (TEOS). The reactor was designed to produce aerosolized nanoparticles at two different particle size ranges, namely d(50) = approximately 30 nm and d(50) = approximately 80 nm; at particle concentrations ranging from 10(7) to 10(8) particles/cm(3). AS particle aerosol concentrations were consistently generated by the reactor. One- or 3-day aerosol exposures produced no significant pulmonary inflammatory, genotoxic, or adverse lung histopathological effects in rats exposed to very high particle numbers corresponding to a range of mass concentrations (1.8 or 86 mg/m(3)). Although the present study was a short-term effort, the methodology described herein can be utilized for longer-term inhalation toxicity studies in rats such as 28-day or 90-day studies. The expansion of the concept to subchronic studies is practical, due, in part, to the consistency of the nanoparticle generation method.

  17. Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.

    PubMed

    Brocklebank, D; Ram, F; Wright, J; Barry, P; Cates, C; Davies, L; Douglas, G; Muers, M; Smith, D; White, J

    2001-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are common diseases of the airways and lungs that have a major impact on the health of the population. The mainstay of treatment is by inhalation of medication to the site of the disease process. This can be achieved by a number of different device types, which have wide variations in costs to the health service. A number of different inhalation devices are available. The pressurised metered-dose inhaler (pMDI) is the most commonly used and cheapest device, which may also be used in conjunction with a spacer device. Newer chlorofluorocarbons (CFC)-free inhaler devices using hydrofluoroalkanes (HFAs) have also been developed. The drug is dissolved or suspended in the propellant under pressure. When activated, a valve system releases a metered volume of drug and propellant. Other devices include breath-actuated pMDIs (BA-pMDI), such as Autohaler and Easi-Breathe. They incorporate a mechanism activated during inhalation that triggers the metered-dose inhaler. Dry powder inhalers (DPI), such as Turbohaler, Diskhaler, Accuhaler and Rotahaler, are activated by inspiration by the patient. The powdered drug is dispersed into particles by the inspiration. With nebulisers oxygen, compressed air, or ultrasonic power is used to break up solutions or suspensions of medication into droplets for inhalation. The aerosol is administered by mask or by a mouthpiece. There has been no previous systematic review of the evidence of clinical effectiveness and cost-effectiveness of these different inhaler devices. To review systematically the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD. The different aspects of inhaler devices were separated into the most clinically relevant comparisons. Methods involved systematic searching of electronic databases and bibliographies for randomised controlled trials (RCTs) and systematic reviews. Pharmaceutical companies and experts in the field were contacted

  18. Safety and pharmacokinetics of ciprofloxacin dry powder for inhalation in cystic fibrosis: a phase I, randomized, single-dose, dose-escalation study.

    PubMed

    Stass, Heino; Delesen, Heinz; Nagelschmitz, Johannes; Staab, Doris

    2015-04-01

    Reliable, reproducible deposition to the lung is a major prerequisite for the clinical use of inhaled drugs. Ciprofloxacin dry powder for inhalation (ciprofloxacin DPI; Bayer HealthCare AG, Leverkusen, Germany) is an antibacterial therapy in development using Novartis' PulmoSphere™ technology (Novartis Pharma AG, Basel, Switzerland) for the targeted delivery of ciprofloxacin to the lung via a T-326 inhaler. This randomized, single-blind, placebo-controlled, dose-escalation study investigated the safety, tolerability, and pharmacokinetics of single-dose ciprofloxacin DPI (32.5 mg [n=6] or 65 mg [n=6]) and matching placebo (n=4) in adult patients with cystic fibrosis and stable pulmonary status (forced expiratory volume in 1 sec ≥30%) who were colonized with Pseudomonas aeruginosa. Peak sputum concentrations of 34.9 mg/L (range 2.03-229) and 376 mg/L (8.95-1283) for ciprofloxacin 32.5 mg and 65 mg, respectively, indicated targeting of ciprofloxacin DPI to the lung. This contrasted with low systemic exposure (peak plasma concentrations: 0.0790 mg/L [32.5 mg] and 0.182 mg/L [65 mg]). Single-dose ciprofloxacin DPI 32.5 mg or 65 mg was well tolerated with similar incidences of adverse events across all groups. No deaths, discontinuations, treatment-related serious adverse events, or clinically relevant changes in laboratory parameters, vital signs, or lung function tests were reported. Lung targeting with high pulmonary concentrations of ciprofloxacin combined with low systemic exposure was confirmed. These results support further study of ciprofloxacin DPI as a potentially more convenient alternative to nebulized antibiotic solutions for managing chronic lung infections.

  19. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

    PubMed

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

    2014-01-01

    Retinal ischemia and reper