Inhaled antibiotics for lower airway infections.

PubMed

Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

2014-03-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

The effect of the medicine administration route on health-related quality of life: Results from a time trade-off survey in patients with bipolar disorder or schizophrenia in 2 Nordic countries.

PubMed

Jørgensen, Tine Rikke; Emborg, Charlotte; Dahlen, Karianne; Bøgelund, Mette; Carlborg, Andreas

2016-07-16

Agitation episodes are common among patients with schizophrenia or bipolar disorder. Oral and intramuscular administration methods are commonly used in pharmacological treatment of acute agitation. Recently, an innovative inhalation product with loxapine(Adasuve®)has become available for treatment of acute agitation episodes associated with bipolar disorder or schizophrenia. The objective for the present study was to investigate the impact of the pharmacological treatment's administration methods on the health-related quality of life (HRQoL) in patients with bipolar disorder or schizophrenia in Denmark and Sweden using a time trade-off (TTO) approach. The TTO methodology was used to examine the HRQoL impact of administration method of pharmacological treatment of acute agitation. Data were collected via an internet-based survey, using an existing panel of respondents with schizophrenia or bipolar disorder. Respondents considered living with schizophrenia/ bipolar disorder, having one yearly agitation episode treated with inhaler better than living with the same conditions and receiving treatment with tablet or injection. The utility value was 0.762 for inhalable treatment, 0.707 for injection and 0.734 for tablet treatment. Patients' preference for treatment delivery options showed that inhalation was associated with a significant utility gain when compared to injection or tablets. Inhalable loxapine may be a new tool for control of agitation episodes for strengthening the patient provider alliance when taking patient's preference for delivery method into consideration.

Quit Intentions Moderate Subjective and Physiological Responses to Acute Nicotine Replacement Therapy Administration in Dependent Smokers.

PubMed

Schlagintweit, Hera E; Campbell, Niamh K; Barrett, Sean P

2017-08-01

This study assessed the impact of expectancy and administration components of acute nicotine inhaler use on craving, heart rate, and smoking behavior in smokers with varying intentions to quit. 47 dependent smokers that differed in self-reported intention to quit (no intention to quit during the next month N = 26 vs. intention to initiate a quit attempt within 2 weeks N = 21) were randomly administered a 4 mg nicotine or nicotine-free inhaler across two sessions. Instructions regarding the inhaler's nicotine content (expect nicotine vs. expect nicotine-free; nicotine expectancy) and flavor (mint vs. citrus) varied across sessions. Craving and heart rate were assessed before and after inhaler administration (two-second inhalations every 10 seconds over 20 minutes). Next, participants were offered an opportunity to self-administer puffs of their preferred tobacco brand during an hour-long progressive ratio task. Across participants, nicotine expectancy independently reduced withdrawal related craving (p = .018), but no comparable effects of nicotine administration were evident. In quitting motivated smokers, nicotine expectancy and administration interacted to reduce intention to smoke (p = .040), while nicotine expectancy (p = .047) and administration (p = .025) independently reduced intention to smoke in quitting unmotivated smokers. Blunted heart rate reactivity to nicotine administration was observed in quitting motivated relative to unmotivated smokers (p = .042); however, neither expectancy nor administration impacted smoking behavior in either group (p values > .25). Findings indicate that participant quitting intentions moderate acute nicotine replacement therapy responses. In quitting motivated smokers, a combination of pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving. Findings from this study demonstrate that motivations to quit smoking moderate subjective and physiological responses to acute nicotine administration and expectancy in dependent cigarette smokers. Quitting motivated smokers showed blunted heart rate reactivity to nicotine administration, suggesting that they may be less sensitive to the rewarding aspects of nicotine consumption. Nicotine administration and expectancy were found to interact to reduce craving in quitting motivated but not in unmotivated smokers, suggesting that pharmacological and psychological factors may be necessary for nicotine replacement therapy to impact craving in smokers who plan to quit. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biokinetics and effects of titania nano-material after inhalation and i.v. injection

NASA Astrophysics Data System (ADS)

Landsiedel, Robert; Fabian, Eric; Ma-Hock, Lan; Wiench, Karin; van Ravenzwaay, Bennard

2009-05-01

Within NanoSafe2 we developed a special inhalation model to investigate deposition of inhaled particles in the lung and the further distribution in the body after. Concurrently, the effects of the inhaled materials in the lung were examined. The results for nano-Titania were compared to results from inhalation studies with micron-sized (non-nano) Titania particles and to quartz particles (DQ12, known to be potent lung toxicants). To build a PBPK model for nano-Titania the tissue distribution of the material was also examined following intravenous (i.v.) administration.

Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.

PubMed

Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kunz, Christina; Formella, Stephan; Kloft, Charlotte

2016-03-01

Olodaterol, a novel β2-adrenergic receptor agonist, is a long-acting, once-daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate. Plasma and urine data after intravenous administration (0.5-25 μg) and oral inhalation (2.5-70 μg via the Respimat® inhaler) were available from a total of 148 healthy volunteers (single and multiple dosing). A stepwise model building approach was applied, using population pharmacokinetic modelling. Systemic disposition parameters were fixed to estimates obtained from intravenous data when modelling data after inhalation. A pharmacokinetic model, including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four-compartment body model (systemic disposition model), was found to describe the data the best. The dose reaching the lung (pulmonary bioavailable fraction) was estimated to be 49.4% [95% confidence interval (CI) 46.1, 52.7%] of the dose released from the device. A large proportion of the pulmonary bioavailable fraction [70.1% (95% CI 66.8, 73.3%)] was absorbed with a half-life of 21.8 h (95% CI 19.7, 24.4 h). The plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers were adequately described. The key finding was that a high proportion of the pulmonary bioavailable fraction had an extended pulmonary residence time. This finding was not expected based on the physicochemical properties of olodaterol. © 2015 The British Pharmacological Society.

Inhalation Toxicology. VI. Evaluation of the Relative Toxicity of Thermal Decomposition Products from Nine Aircraft Panel Materials.

DTIC Science & Technology

1986-02-01

AD-R168 250 INHALATION TOXICOLOGY VI EVALUATION OF THE RELATIVE i/I TOXICITY OF THERMAL D. (U) FEDERAL AVIATION ADMINISTRATION WASHINGTON DC OFFICE...FAA/AM-8613 INHALATION TOXICOLOGY : (0 Office of Aviation Medicine Vi. Evaluation of the Relative Washington, D.C. 20591 Toxicity of Thermal...Government Accession No. 3. Recipient’s Catalog No. /XO/FAA/AM-86/3 /1j, 14 4F d Y_0 4. Title and Subtitle 5. Report Date INHALATION TOXICOLOGY : VI

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

PubMed

2016-02-08

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

Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice.

PubMed

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

2016-06-01

Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

ELECTROCARDIOGRAPHIC CHANGES IN RABBITS SUBJECTED TO THE CHRONIC ACTION OF RADIOACTIVE ZINC DURING INTRAVENOUS ADMINISTRATION OF ADRENALINE AND INHALATION OF AMMONIA (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ovakimov, V.G.; Bibikhin, L.N.; Saitanov, A.O.

1963-09-01

The employment of pharmacological loadings (administration of adrenaline and inhalation of ammonia) in rabbits subjected to the chronic action of radioactive zinc (1 and 10 mu C/kg) disclosed changes in the sensitivity of adrenoreactive systems of the myocardium (in adrenaline test) and an altered intensity and duration of reflex bradycardia (in ammonia test). (auth)

Prevention of the pulmonary vasoconstrictor effects of HBOC-201 in awake lambs by continuously breathing nitric oxide.

PubMed

Yu, Binglan; Volpato, Gian Paolo; Chang, Keqin; Bloch, Kenneth D; Zapol, Warren M

2009-01-01

Hemoglobin-based oxygen-carrying solutions (HBOC) provide emergency alternatives to blood transfusion to carry oxygen to tissues without the risks of disease transmission or transfusion reaction. Two primary concerns hampering the clinical acceptance of acellular HBOC are the occurrence of systemic and pulmonary vasoconstriction and the maintenance of the heme-iron in the reduced state (Fe2+). We recently demonstrated that pretreatment with inhaled nitric oxide prevents the systemic hypertension induced by HBOC-201 (polymerized bovine hemoglobin) infusion in awake mice and sheep without causing methemoglobinemia. However, the impact of HBOC-201 infusion with or without inhaled nitric oxide on pulmonary vascular tone has not yet been examined. The pulmonary and systemic hemodynamic effects of breathing nitric oxide both before and after the administration of HBOC-201 were determined in healthy, awake lambs. Intravenous administration of HBOC-201 (12 ml/kg) induced prolonged systemic and pulmonary vasoconstriction. Pretreatment with inhaled nitric oxide (80 parts per million [ppm] for 1 h) prevented the HBOC-201--induced increase in mean arterial pressure but not the increase of pulmonary arterial pressure, systemic vascular resistance, or pulmonary vascular resistance. Pretreatment with inhaled nitric oxide (80 ppm for 1 h) followed by breathing a lower concentration of nitric oxide (5 ppm) during and after HBOC-201 infusion prevented systemic and pulmonary vasoconstriction without increasing methemoglobin levels. These findings demonstrate that pretreatment with inhaled nitric oxide followed by breathing a lower concentration of the gas during and after administration of HBOC-201 may enable administration of an acellular hemoglobin substitute without vasoconstriction while preserving its oxygen-carrying capacity.

Inhalation of Nebulized Perfluorochemical Enhances Recombinant Adenovirus and Adeno-Associated Virus-Mediated Gene Expression in Lung Epithelium

PubMed Central

Beckett, Travis; Bonneau, Laura; Howard, Alan; Blanchard, James; Borda, Juan; Weiner, Daniel J.; Wang, Lili; Gao, Guang Ping; Kolls, Jay K.; Bohm, Rudolf; Liggitt, Denny

2012-01-01

Abstract Use of perfluorochemical liquids during intratracheal vector administration enhances recombinant adenovirus and adeno-associated virus (AAV)-mediated lung epithelial gene expression. We hypothesized that inhalation of nebulized perfluorochemical vapor would also enhance epithelial gene expression after subsequent intratracheal vector administration. Freely breathing adult C57BL/6 mice were exposed for selected times to nebulized perflubron or sterile saline in a sealed Plexiglas chamber. Recombinant adenoviral vector was administered by transtracheal puncture at selected times afterward and mice were killed 3 days after vector administration to assess transgene expression. Mice tolerated the nebulized perflubron without obvious ill effects. Vector administration 6 hr after nebulized perflubron exposure resulted in an average 540% increase in gene expression in airway and alveolar epithelium, compared with that with vector alone or saline plus vector control (p<0.05). However, vector administration 1 hr, 1 day, or 3 days after perflubron exposure was not different from either nebulized saline with vector or vector alone and a 60-min exposure to nebulized perflubron is required. In parallel pilot studies in macaques, inhalation of nebulized perflubron enhanced recombinant AAV2/5 vector expression throughout the lung. Serial chest radiographs, bronchoalveolar lavages, and results of complete blood counts and serum biochemistries demonstrated no obvious adverse effects of nebulized perflubron. Further, one macaque receiving nebulized perflubron only was monitored for 1 year with no obvious adverse effects of exposure. These results demonstrate that inhalation of nebulized perflubron, a simple, clinically more feasible technique than intratracheal administration of liquid perflubron, safely enhances lung gene expression. PMID:22568624

Development of an Inhaled Dry-Powder Formulation of Tobramycin Using PulmoSphere™ Technology

PubMed Central

Weers, Jeffry; Heuerding, Silvia

2011-01-01

Abstract At present, the only approved inhaled antipseudomonal antibiotics for chronic pulmonary infections in patients with cystic fibrosis (CF) are nebulized solutions. However, prolonged administration and cleaning times, high administration frequency, and cumbersome delivery technologies with nebulizers add to the high treatment burden in this patient population. PulmoSphere™ technology is an emulsion-based spray-drying process that enables the production of light porous particle, dry-powder formulations, which exhibit improved flow and dispersion from passive dry powder inhalers. This review explores the fundamental characteristics of PulmoSphere technology, focusing on the development of a dry powder formulation of tobramycin for the treatment of chronic pulmonary Pseudomonas aeruginosa (Pa) infection in CF patients. This dry powder formulation provides substantially improved intrapulmonary deposition efficiency, faster delivery, and more convenient administration over nebulized formulations. The availability of more efficient and convenient treatment options may improve treatment compliance, and thereby therapeutic outcomes in CF. PMID:21395432

Evaluation of Inhaled Dornase Alfa Administration in Non-Cystic Fibrosis Patients at a Tertiary Academic Medical Center.

PubMed

Torbic, Heather; Hacobian, Gaspar

2016-10-01

The use of dornase alfa in a non-cystic fibrosis population has been proposed to help improve atelectasis and secretions. Data evaluating dornase alfa in a non-cystic fibrosis population are limited, and the prescribing practices at a tertiary academic medical center are unknown. Adult patients ≥18 years of age were included if they received inhaled dornase alfa. Patients were excluded if they had cystic fibrosis. Data collected included demographic data, dornase alfa prescribing patterns, concomitant inhaled therapy, blood gas data, and documented efficacy and safety data. Seventy-six orders for dornase alfa therapy were included in the analysis. Of the patients, 18% had asthma and 19% had chronic obstructive pulmonary disease. Seventy-seven percent of the patients received concomitant inhaled therapy. Eighty-three percent of orders were for 2.5 mg of dornase alfa twice daily. The median (interquartile range [IQR]) number of doses received per patient was 6 (4-13) with a median (IQR) duration of 3 (2-7) days. After inhaled dornase alfa administration, 11% of patients were able to cough productively. No safety issues related to inhaled dornase alfa therapy were noted. Inhaled dornase alfa is commonly prescribed to improve atelectasis and secretions in a non-cystic fibrosis patient population at a tertiary academic medical center. © The Author(s) 2015.

Development of an Improved Inhalable Powder Formulation of Pirfenidone by Spray-Drying: In Vitro Characterization and Pharmacokinetic Profiling.

PubMed

Seto, Yoshiki; Suzuki, Gen; Leung, Sharon Shui Yee; Chan, Hak-Kim; Onoue, Satomi

2016-06-01

Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations. Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose. SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.

Inhaled delivery of Δ(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology.

PubMed

Nguyen, Jacques D; Aarde, Shawn M; Vandewater, Sophia A; Grant, Yanabel; Stouffer, David G; Parsons, Loren H; Cole, Maury; Taffe, Michael A

2016-10-01

Most human Δ(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non-combusted methods for the inhalation of psychoactive drugs (Volcano(®), e-cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ∼40 min of exposure, was of comparable magnitude (∼3 °Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.

PubMed

de Berardis, Domenico; Fornaro, Michele; Orsolini, Laura; Iasevoli, Felice; Tomasetti, Carmine; de Bartolomeis, Andrea; Serroni, Nicola; Valchera, Alessandro; Carano, Alessandro; Vellante, Federica; Marini, Stefano; Piersanti, Monica; Perna, Giampaolo; Martinotti, Giovanni; Di Giannantonio, Massimo

2017-02-08

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2015-03-01

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

Optimizing inhaler use by pharmacist-provided education to community-dwelling elderly.

PubMed

Bouwmeester, Carla; Kraft, Jacqueline; Bungay, Kathleen M

2015-10-01

To assess, using a standard observational tool, the ability of patients to demonstrate and maintain proper inhaled medication administration techniques following pharmacist education. Six-month observational study. Patients' homes or adult day health center. Patients in a Program for All-inclusive Care for the Elderly (PACE) prescribed one or more inhaled medications used at least once daily. Instruction by on-site clinical pharmacist. Hickey's Pharmacies Inhaler Technique assessment (score range: 0-20, higher better). Forty-two patients were evaluated at baseline, taught proper techniques for using inhaled medications, assessed immediately following the education, and re-assessed 4-6 weeks later. The mean pre-assessment score was 14 (SD 4.5, range 0-20), the initial post-assessment score increased to 18 (SD 3, range 10-20). The second post-assessment (4-6 weeks later) score mean was 17.7 (SD 3, range 10-20). Both follow-up scores were significantly improved from baseline (p < 0.05). Multivariable analysis indicated the strongest predictors of second post-training score were: score after initial pharmacist training and being subscribed to auto-refill. These characteristics predicted ∼70% of the variance in the second score (p < 0.001). These results indicate that education by a pharmacist combined with an auto-refill program can improve and sustain appropriate inhaler use by community-dwelling elders in a PACE program. The improved score was maintained 4-6 weeks later indicating a sustained benefit of medication administration education. Optimal inhaler use ensures optimal dosing and supports appropriate inhaler treatment in lieu of oral agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Population pharmacokinetics of caffeine and its metabolites theobromine, paraxanthine and theophylline after inhalation in combination with diacetylmorphine.

PubMed

Zandvliet, Anthe S; Huitema, Alwin D R; de Jonge, Milly E; den Hoed, Rob; Sparidans, Rolf W; Hendriks, Vincent M; van den Brink, Wim; van Ree, Jan M; Beijnen, Jos H

2005-01-01

The stimulant effect of caffeine, as an additive in diacetylmorphine preparations for study purposes, may interfere with the pharmacodynamic effects of diacetylmorphine. In order to obtain insight into the pharmacology of caffeine after inhalation in heroin users, the pharmacokinetics of caffeine and its dimethylxanthine metabolites were studied. The objectives were to establish the population pharmacokinetics under these exceptional circumstances and to compare the results to published data regarding intravenous and oral administration in healthy volunteers. Diacetylmorphine preparations containing 100 mg of caffeine were used by 10 persons by inhalation. Plasma concentrations of caffeine, theobromine, paraxanthine and theophylline were measured by high performance liquid chromatography. Non-linear mixed effects modelling was used to estimate population pharmacokinetic parameters. The model was evaluated by the jack-knife procedure. Caffeine was rapidly and effectively absorbed after inhalation. Population pharmacokinetics of caffeine and its dimethylxanthine metabolites could adequately and simultaneously be described by a linear multi-compartment model. The volume of distribution for the central compartment was estimated to be 45.7 l and the apparent elimination rate constant of caffeine at 8 hr after inhalation was 0.150 hr(-1) for a typical individual. The bioavailability was approximately 60%. The presented model adequately describes the population pharmacokinetics of caffeine and its dimethylxanthine metabolites after inhalation of the caffeine sublimate of a 100 mg tablet. Validation proved the stability of the model. Pharmacokinetics of caffeine after inhalation and intravenous administration are to a large extent similar. The bioavailability of inhaled caffeine is approximately 60% in experienced smokers.

Protective effects of radon inhalation on carrageenan-induced inflammatory paw edema in mice.

PubMed

Kataoka, Takahiro; Teraoka, Junichi; Sakoda, Akihiro; Nishiyama, Yuichi; Yamato, Keiko; Monden, Mayuko; Ishimori, Yuu; Nomura, Takaharu; Taguchi, Takehito; Yamaoka, Kiyonori

2012-04-01

We assessed whether radon inhalation inhibited carrageenan-induced inflammation in mice. Carrageenan (1% v/v) was injected subcutaneously into paws of mice that had or had not inhaled approximately 2,000 Bq/m(3) of radon for 24 h. Radon inhalation significantly increased superoxide dismutase (SOD) and catalase activities and significantly decreased lipid peroxide levels in mouse paws, indicating that radon inhalation activates antioxidative functions. Carrageenan administration induced paw edema and significantly increased tumor necrosis factor-alpha (TNF-α) and nitric oxide in serum. However, radon inhalation significantly reduced carrageenan-induced paw edema. Serum TNF-α levels were lower in the radon-treated mice than in sham-treated mice. In addition, SOD and catalase activities in paws were significantly higher in the radon-treated mice than in the sham-treated mice. These findings indicated that radon inhalation had anti-inflammatory effects and inhibited carrageenan-induced inflammatory paw edema.

An evaluation of children's metered-dose inhaler technique for asthma medications.

PubMed

Burkhart, Patricia V; Rayens, Mary Kay; Bowman, Roxanne K

2005-03-01

Regardless of the medication delivery system, health care providers need to teach accurate medication administration techniques to their patients, educate them about the particular nuances of the prescribed delivery system (eg, proper storage), and reinforce these issues at each health encounter. A single instruction session is not sufficient to maintain appropriate inhaler techniques for patients who require continued use. Providing written steps for the administration technique is helpful so that the patient can refer to them later when using the medication. The National Heart, Lung, and Blood Institute's "Practical Guide for the Diagnosis and Management of Asthma" recommends that practitioners follow these steps for effective inhaler technique training when first prescribing an inhaler: 1. Teach patients the steps and give written instruction handouts. 2. Demonstrate how to use the inhaler step-by-step. 3. Ask patients to demonstrate how to use the inhaler. Let the patient refer to the handout on the first training. Then use the handout asa checklist to assess the patient's future technique. 4. Provide feedback to patients about what they did right and what they need to improve. Have patients demonstrate their technique again, if necessary. The last two steps should be performed (ie, demonstration and providing feedback on what patients did right and what they need to improve) at every subsequent visit. If the patient makes multiple errors, it is advisable to focus on improving one or two key steps at a time. With improvements in drug delivery come challenges, necessitating that practitioners stay current with new medication administration techniques. Teaching and reinforcing accurate technique at each health care encounter are critical to help ensure medication efficacy for patients with asthma. Since one fifth of children in the study performed incorrect medication technique even after education, checklists of steps for the correct use of inhalation devices, such as those provided in this article, should be given to patients for home use and for use by clinicians to evaluate patient technique at each health encounter.

Macrophages as key elements of Mixed-oxide [U-Pu(O2)] distribution and pulmonary damage after inhalation?

PubMed

Van der Meeren, Anne; Moureau, Agnes; Griffiths, Nina M

2014-11-01

Abstract Purpose: To investigate the consequences of alveolar macrophage (AM) depletion on Mixed OXide fuel (MOX: U, Pu oxide) distribution and clearance, as well as lung damage following MOX inhalation. Rats were exposed to MOX by nose only inhalation. AM were depleted with intratracheal administration of liposomal clodronate at 6 weeks. Lung changes, macrophage activation, as well as local and systemic actinide distribution were studied up to 3 months post-inhalation. Clodronate administration modified excretion/retention patterns of α activity. At 3 months post-inhalation lung retention was higher in clodronate-treated rats compared to Phosphate Buffered Saline (PBS)-treated rats, and AM-associated α activity was also increased. Retention in liver was higher in clodronate-treated rats and fecal and urinary excretions were lower. Three months after inhalation, rats exhibited lung fibrotic lesions and alveolitis, with no marked differences between the two groups. Foamy macrophages of M2 subtype [inducible Nitric Oxide Synthase (iNOS) negative but galectin-3 positive] were frequently observed, in correlation with the accumulation of MOX particles. AM from all MOX-exposed rats showed increased chemokine levels as compared to sham controls. Despite the transient reduced AM numbers in clodronate-treated animals no major differences on lung damage were observed as compared to non-treated rats after MOX inhalation. The higher lung activity retention in rats receiving clodronate seems to be part of a general inflammatory response and needs further investigation.

The accuracy of burn diagnosis codes in health administrative data: A validation study.

PubMed

Mason, Stephanie A; Nathens, Avery B; Byrne, James P; Fowler, Rob; Gonzalez, Alejandro; Karanicolas, Paul J; Moineddin, Rahim; Jeschke, Marc G

2017-03-01

Health administrative databases may provide rich sources of data for the study of outcomes following burn. We aimed to determine the accuracy of International Classification of Diseases diagnoses codes for burn in a population-based administrative database. Data from a regional burn center's clinical registry of patients admitted between 2006-2013 were linked to administrative databases. Burn total body surface area (TBSA), depth, mechanism, and inhalation injury were compared between the registry and administrative records. The sensitivity, specificity, and positive and negative predictive values were determined, and coding agreement was assessed with the kappa statistic. 1215 burn center patients were linked to administrative records. TBSA codes were highly sensitive and specific for ≥10 and ≥20% TBSA (89/93% sensitive and 95/97% specific), with excellent agreement (κ, 0.85/κ, 0.88). Codes were weakly sensitive (68%) in identifying ≥10% TBSA full-thickness burn, though highly specific (86%) with moderate agreement (κ, 0.46). Codes for inhalation injury had limited sensitivity (43%) but high specificity (99%) with moderate agreement (κ, 0.54). Burn mechanism had excellent coding agreement (κ, 0.84). Administrative data diagnosis codes accurately identify burn by burn size and mechanism, while identification of inhalation injury or full-thickness burns is less sensitive but highly specific. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Research Summaries of 1989

DTIC Science & Technology

1989-01-01

INHALATION AND DERMAL EXPOSURE. NMRI REPORT. JULY 1989. 34 PP. TOXICOLOGY DETACHMENT M0096.00O.0006 (DW377025) REPORT NO.35 ADMINISTRATION INHALATION ...672 NMRI 89-0122 MADONNA GS LEDNEY GD ELLIOTT TB BROOK I ULRICH JT qYERS KR PATCHEN ML WALKER RI TREHALOSE DIMYCOLATE ENHANCES RESISTANCE TO INFECTION

In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection.

PubMed

Marshell, R; Kearney-Ramos, T; Brents, L K; Hyatt, W S; Tai, S; Prather, P L; Fantegrossi, W E

2014-09-01

Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke these drugs, but preclinical studies usually rely on injection for drug delivery. We used the cannabinoid tetrad and drug discrimination to compare in vivo effects of inhaled drugs with injected doses of these two SCBs, as well as with the phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Mice inhaled various doses of Δ(9)-THC, JWH-018 or JWH-073, or were injected intraperitoneally (IP) with these same compounds. Rectal temperature, tail flick latency in response to radiant heat, horizontal bar catalepsy, and suppression of locomotor activity were assessed in each animal. In separate studies, mice were trained to discriminate Δ(9)-THC (IP) from saline, and tests were performed with inhaled or injected doses of the SCBs. Both SCBs elicited Δ(9)-THC-like effects across both routes of administration, and effects following inhalation were attenuated by pretreatment with the CB1 antagonist/inverse agonist rimonabant. No cataleptic effects were observed following inhalation, but all compounds induced catalepsy following injection. Injected JWH-018 and JWH-073 fully substituted for Δ(9)-THC, but substitution was partial (JWH-073) or required relatively higher doses (JWH-018) when drugs were inhaled. These studies demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor-mediated Δ(9)-THC-like effects in mice when delivered via inhalation or via injection. Across these routes of administration, differences in cataleptic effects and, perhaps, discriminative stimulus effects, may implicate the involvement of active metabolites of these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhaled sildenafil nanocomposites: lung accumulation and pulmonary pharmacokinetics.

PubMed

Ghasemian, Elham; Vatanara, Alireza; Rouini, Mohammad Reza; Rouholamini Najafabadi, Abdolhossein; Gilani, Kambiz; Lavasani, Hoda; Mohajel, Nasir

2016-12-01

Administration of sildenafil citrate (SC) is considered as a strategy in the treatment of pulmonary hypertension. This study reports production of the inhalable microparticles containing SC-loaded poly(lactide-co-glycolic acid)-nanoparticles. SC-nanoparticles were prepared by the double emulsion solvent evaporation method. Next, free SC and SC-loaded nanoparticles were spray dried in the presence of appropriate excipients (lactose, maltose and trehalose). Physicochemical properties and aerodynamic behavior of prepared powders were evaluated. In addition, drug accumulation from selected formulations in the rat lung tissue was compared with oral and IV administration. Size and fine particle fraction of selected nanocomposites and free SC microparticles were 7 and 4.5 µm, and 60.2% and 68.2%, respectively. Following oral and IV administration, the drug was not detectable in the lung after 4 and 6 h, respectively, but in SC-loaded nanoparticles, the drug was detectable in the lung even after 12 h of inhalation. Respirable particles containing free SC provided high concentration at first that was detectable up to 6 after insufflation. In vivo study demonstrated that pulmonary administration of sildenafil and sildenafil nanoparticles produced longer half-life and higher concentration of the drug in the lung tissue as compared to oral and IV administration. So, these formulations could be more effective than oral and IV administration of this drug.

Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.

PubMed

Wlaź, Piotr; Knaga, Sebastian; Kasperek, Kornel; Wlaź, Aleksandra; Poleszak, Ewa; Jeżewska-Witkowska, Grażyna; Winiarczyk, Stanisław; Wyska, Elżbieta; Heinekamp, Thorsten; Rundfeldt, Chris

2015-08-01

Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.

Stimulus properties of inhaled substances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R.W.

1978-10-01

Inhaled substances can modify behavior by their toxic action, or because they are discriminable events, or because they can support or suppress behavior. They can be used as discriminative stimuli at concentrations above the olfactory threshold. Inhalants can elicit unconditioned reflexes. As aversive stimuli, they can be studied in respondent conditioning experiments (e.g. conditioned suppression), in punishment paradigms, or as negative reinforcers in escape paradigms. Inhalants can also be positive reinforcers; their intoxication properties have engendered patterns of chronic self-administration (solvent abuse). Such stimulus properties should be considered in industrial hygiene and environmental quality decisions. Laboratory techniques to study suchmore » properties abound.« less

Stimulus properties of inhaled substances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R.W.

1978-01-01

Inhaled substances can modify behavior by their toxic action, or because they are discriminable events, or because they can support or suppress behavior. They can be used as discriminative stimuli at concentrations above the olfactory threshold. Inhalants can elicit unconditioned reflexes. As aversive stimuli, they can be studied in respondent conditioning experiments (e.g. conditioned suppression), in punishment paradigms, or as negative reinforcers in escape paradigms. Inhalants can also be positive reinforcers; their intoxicating properties have engendered patterns of chronic self-administration (solvent abuse). Such stimulus properties should be considered in industrial hygiene and environmental quality decisions. Laboratory techniques to study suchmore » properties abound.« less

Comparison of the protective effect of formoterol and of salmeterol against exercise-induced bronchospasm when given immediately before a cycloergometric test.

PubMed

Ferrari, Marcello; Segattini, Carlo; Zanon, Roberto; Bertaiola, Mariano; Balestreri, Filippo; Brotto, Emanuele; Lo Cascio, Vincenzo

2002-01-01

Salmeterol and formoterol, two long-acting beta(2)-adrenergic agonists, have been shown to be effective against exercise-induced bronchospasm (EIB) several hours after inhalation, but no study has yet compared their protective effect immediately after administration. To compare the protective effect of inhaled formoterol and salmeterol against EIB immediately and 4 h after administration. Double-blind, two-period cross-over study of 11 EIB-positive asthmatic subjects (mean age 21.2 years) administered formoterol 24 microg and salmeterol 50 microg by means of metered-dose inhalers (MDIs) on 2 days separated by an interval of 72 h; the subjects performed two cycloergometric exercise tests immediately and 4 h after dosing. Forced expiratory volume (FEV(1)) measurements were made before and at the end of exercise, and then after 3, 5, 10, 15, 20, 25 and 30 min. The maximum percentage decrease in FEV(1) in the 30 min following exercise was considered. Immediately after drug administration, but not 4 h later, formoterol provided significantly better protection against EIB than salmeterol (p = 0.02). The number of formoterol-treated subjects protected against EIB (i.e. with a <15% decrease in FEV(1) after treatment) was 10/11 after the first exercise test and 7/8 after the second; the corresponding figures after salmeterol treatment were 5/11 and 7/8. Our results show that formoterol inhaled via an MDI is effective in preventing EIB as early as within a few minutes of administration, whereas salmeterol does not offer any appreciable protection. On the contrary, the protective effect of the two drugs is clinically equivalent 4 h after administration. Copyright 2002 S. Karger AG, Basel

Use of cyanide antidotes in burn patients with suspected inhalation injuries in North America: a cross-sectional survey.

PubMed

Dumestre, Danielle; Nickerson, Duncan

2014-01-01

This study aimed to assess the use of cyanide antidotes and the determine the opinion on empiric administration of hydroxocobalamin in North American burn patients with suspected smoke inhalation injuries. An online cross-sectional survey was sent to directors of 90 major burn centers in North America, which were listed on the American Burn Association Web site. A multiple-choice format was used to determine the percentage of patients tested for cyanide poisoning on admission, the current administration of a cyanide antidote based solely on clinical suspicion of poisoning, and the antidote used. To ascertain views on immediate administration of hydroxocobalamin before confirmation of cyanide poisoning an option was included to expand the response in written format. Twenty-nine of 90 burn directors (32%) completed the survey. For the population of interest, the majority of burn centers (59%) do not test for cyanide poisoning on admission and do not administer an antidote based solely on clinical suspicion of cyanide poisoning (58%). The most commonly available antidote is hydroxocobalamin (50%), followed by the cyanide antidote kit (29%). The opinion regarding instant administration of hydroxocobalamin when inhalation injury is suspected is mixed: 31% support its empiric use, 17% do not, and the remaining 52% have varying degrees of confidence in its utility. In North America, most patients burnt in closed-space fires with inhalation injuries are neither tested for cyanide poisoning in a timely manner nor empirically treated with a cyanide antidote. Although studies have shown the safety and efficacy of empiric and immediate administration of hydroxocobalamin, most centers are not willing to do so.

A brief history of inhaled asthma therapy over the last fifty years.

PubMed

Crompton, Graham

2006-12-01

This year is the 50th anniversary of the introduction into clinical use of the first modern inhaler for the management of asthma--the pressurised metered-dose inhaler (pMDI). The pMDI was initially used for the administration of the non-selective beta-agonists adrenaline and isoprenaline. However, the epidemic of asthma deaths which occurred in the 1960s led to these drugs being superseded by the selective short-acting beta-agonist salbutamol, and the first inhaled corticosteroid (ICS) beclomethasone. At the same time, sodium cromoglycate was introduced, to be administered via the first dry-powder inhaler--the Spinhaler--but owing to its relatively weak anti-inflammatory action its use is now very limited. Over the last 10 years, the long-acting beta-agonists (LABAs) have become an important add-on therapy for the management of asthma, and they are now often used with ICS in a single ICS/LABA combination inhaler.

Inhaled antibiotics for lower respiratory tract infections: focus on ciprofloxacin.

PubMed

Serisier, D J

2012-05-01

The administration of antibiotics by the inhaled route offers an appealing and logical approach to treating infectious respiratory conditions. Studies in the cystic fibrosis (CF) population have established the efficacy of this therapeutic concept and inhaled antibiotic therapy is now one of the pillars of management in CF. There are now a number of new inhaled antibiotic formulations that have shown impressive preliminary evidence for efficacy in CF and are commencing phase III efficacy studies. Translation of this paradigm into the non-CF bronchiectasis population has proven difficult thus far, apparently due to problems with tolerability of inhaled formulations. Inhaled versions of ciprofloxacin have shown good tolerability and microbiological efficacy in preliminary studies, suggesting that effective inhaled antibiotics are finally on the horizon for this previously neglected patient population. The increased use of long-term inhaled antibiotics for a wider range of non-CF indications presents risks to the broader community of greater antimicrobial resistance development that must be carefully weighed against any demonstrated benefits. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

Brown adipose tissue thermogenesis does not explain the intra-administration hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide to rats.

PubMed

Al-Noori, Salwa; Ramsay, Douglas S; Cimpan, Andreas; Maltzer, Zoe; Zou, Jessie; Kaiyala, Karl J

2016-08-01

Initial administration of ≥60% nitrous oxide (N2O) to rats promotes hypothermia primarily by increasing whole-body heat loss. We hypothesized that the drug promotes heat loss via the tail and might initially inhibit thermogenesis via brown adipose tissue (BAT), major organs of thermoregulation in rodents. Following repeated administrations, N2O inhalation evokes hyperthermia underlain by increased whole-body heat production. We hypothesized that elevated BAT thermogenesis plays a role in this thermoregulatory sign reversal. Using dual probe telemetric temperature implants and infrared (IR) thermography, we assessed the effects of nine repeated 60% N2O administrations compared to control (con) administrations on core temperature, BAT temperature, lumbar back temperature and tail temperature. Telemetric core temperature, telemetric BAT temperature, and IR BAT temperature were reduced significantly during initial 60% N2O inhalation (p≤0.001 compared to con). IR thermography revealed that acute N2O administration unexpectedly reduced tail temperature (p=0.0001) and also inhibited IR lumbar temperature (p<0.0001). In the 9th session, N2O inhalation significantly increased telemetric core temperature (p=0.007) indicative of a hyperthermic sign reversal, yet compared to control administrations, telemetric BAT temperature (p=0.86), IR BAT temperature (p=0.85) and tail temperature (p=0.47) did not differ significantly. Thus, an initial administration of 60% N2O at 21°C may promote hypothermia via reduced BAT thermogenesis accompanied by tail vasoconstriction as a compensatory mechanism to limit body heat loss. Following repeated N2O administrations rats exhibit a hyperthermic core temperature but a normalized BAT temperature, suggesting induction of a hyperthermia-promoting thermogenic adaptation of unknown origin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation and properties of inhalable nanocomposite particles for treatment of lung cancer.

PubMed

Tomoda, Keishiro; Ohkoshi, Takumi; Hirota, Keiji; Sonavane, Ganeshchandra S; Nakajima, Takehisa; Terada, Hiroshi; Komuro, Masahito; Kitazato, Kenji; Makino, Kimiko

2009-07-01

Nanoparticles have widely been studied in drug delivery research for targeting and controlled release. The aim of this article is application of nanoparticles as an inhalable agent for treatment of lung cancer. To deposit effectively deep the particles in the lungs, the PLGA nanoparticles loaded with the anticancer drug 6-{[2-(dimethylamino)ethyl]amino}-3-hydroxyl-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) were prepared in the form of nanocomposite particles. The nanocomposite particles consist of the complex of drug-loaded nanoparticles and excipients. In this study, the anticancer effects of the nanocomposite particles against the lung cancer cell line A549. Also, the concentration of TAS-103 in blood and lungs were determined after administration of the nanocomposite particles by inhalation to rats. TAS-103-loaded PLGA nanoparticles were prepared with 5% and 10% of loading ratio by spray drying method with trehalose as an excipient. The 5% drug-loaded nanocomposite particles were more suitable for inhalable agent because of the sustained release of TAS-103 and higher FPF value. Cytotoxicity of nanocomposite particles against A549 cells was higher than that of free drug. When the nanocomposite particles were administered in rats by inhalation, drug concentration in lung was much higher than that in plasma. Furthermore, drug concentration in lungs administered by inhalation of nanocomposite particles was much higher than that after intravenous administration of free drug. From these results, the nanocomposite particle systems could be promising for treatment of lung cancer.

Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems

PubMed Central

2016-01-01

Administration of drug molecules by inhalation route for treatment of respiratory diseases has the ability to deliver drugs, hormones, nucleic acids, steroids, proteins, and peptides, particularly to the site of action, improving the efficacy of the treatment and consequently lessening adverse effects of the treatment. Numerous inhalation delivery systems have been developed and studied to treat respiratory diseases such as asthma, COPD, and other pulmonary infections. The progress of disciplines such as biomaterials science, nanotechnology, particle engineering, molecular biology, and cell biology permits further improvement of the treatment capability. The present review analyzes modern therapeutic approaches of inhaled drugs with special emphasis on novel drug delivery system for treatment of various respiratory diseases. PMID:27867663

The prevalence and correlates of buprenorphine inhalation amongst opioid substitution treatment (OST) clients in Australia.

PubMed

Horyniak, Danielle; Dietze, Paul; Larance, Briony; Winstock, Adam; Degenhardt, Louisa

2011-03-01

Diversion and injection of buprenorphine (Subutex(®)) and buprenorphine-naloxone (Suboxone(®)) have been well documented. Recent international research and local anecdotal evidence suggest that these medications are also used by other routes of administration, including smoking and snorting. A cross-sectional sample of 440 opioid substitution treatment (OST) clients was recruited through pharmacies and clinics in three Australian jurisdictions, and interviewed face-to-face using a structured questionnaire. Eligible participants were those aged 18 or over, who had resided in their home state for at least six months, and had been in their current treatment episode for at least 4 weeks. We compared differences in characteristics between clients who had ever inhaled (smoked or snorted) buprenorphine (including buprenorphine-naloxone) and other OST clients. Logistic regression was used to identify correlates of buprenorphine inhalation. Sixty-eight clients who had never used buprenorphine were excluded from analysis. Sixty-five clients (18%) reported having ever inhaled buprenorphine, with Subutex(®) smoking being most common, reported by 50 clients (77%). In multivariable logistic regression, those who reported ever inhaling buprenorphine were significantly more likely to: be aged 35 or younger, have ever been in prison and have ever injected buprenorphine. Clients from New South Wales and Victoria were significantly less likely to have ever inhaled buprenorphine than those from South Australia. Our data indicates that the inhalation of buprenorphine has occurred in a significant minority of Australian OST clients. The motivations, contexts and potential health consequences of buprenorphine use by these atypical routes of administration, particularly in a correctional setting, warrant further exploration. Copyright © 2010 Elsevier B.V. All rights reserved.

Relationship Between Emotional Behavior in Mice and the Concentration of (+)-α-Santalol in the Brain.

PubMed

Satou, Tadaaki; Ogawa, Yuko; Koike, Kazuo

2015-08-01

We previously reported finding anxiolytic-like activity for sandalwood oil after administration in mice. In this report, we further investigated the emotional behavior associated with inhaled or intraperitoneally administered (+)-α-santalol, the main component of sandalwood oil, in addition to examining whether pharmacological or neurological transfers are responsible for this behavior. After administration of (+)-α-santalol by inhalation or intraperitoneal injection, we assessed anxiolytic-like and locomotor activities using elevated-plus maze tests. We also examined the relationship between the emotional behavior and the (+)-α-santalol brain concentration. Anxiolytic-like activity was not observed immediately after administration or after water-immersion stress for 24 h for either the (+)-α-santalol 2 μL/L air inhalation or the (+)-α-santalol 0.03 mL/kg (i.p.) administration. However, mice administered (+)-α-santalol 0.03 mL/kg intraperitoneally exhibited a significant decrease in the locomotor activity after exposure to water-immersion stress for 24 h. The brain (+)-α-santalol concentration was 2.6 µg/g tissue after (+)-α-santalol 0.03 mL/kg (i.p.) administration. The observed shift of (+)-α-santalol to the brain suggests that this component acts via pharmacological transfer and is responsible for the sedative effect but not the anxiolytic-like activity. Copyright © 2015 John Wiley & Sons, Ltd.

Schedules of Controlled Substances: Table of Excluded Nonnarcotic Products: Vicks® VapoInhaler®.

PubMed

2016-02-08

This final rule adopts the interim final rule, with a correction to spelling of the manufacturer's name that was published in the Federal Register on October 27, 2015. The Drug Enforcement Administration is amending the table of Excluded Nonnarcotic Products to update the listing for Vicks® VapoInhaler®, containing 50 mg levmetamfetamine in a nasal decongestant inhaler, marketed by The Procter & Gamble Company. This over-the-counter, non-narcotic drug product is excluded from provisions of the Controlled Substances Act.

Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats.

PubMed

Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M; Garlick, Rhonda B; Rioux, Jacqueline S; Murphy, Angela L; Roe, Gates B; White, Carl W; Veress, Livia A

2018-01-01

Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD 58-67 ) in a whole-body exposure chamber, and given oxygen (0.8 Fi O 2 ) or air (0.21 Fi O 2 ) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

75 FR 31450 - Memorandum of Understanding by and Between the United States Food and Drug Administration and the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... Administration and the International Anesthesia Research Society for the Safety of Key Inhaled and Intravenous Drugs in Pediatrics Public-Private Partnership AGENCY: Food and Drug Administration, HHS. ACTION: Notice... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004...

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation.

PubMed

Kataoka, Takahiro; Sakoda, Akihiro; Yoshimoto, Masaaki; Nakagawa, Shinya; Toyota, Teruaki; Nishiyama, Yuichi; Yamato, Keiko; Ishimori, Yuu; Kawabe, Atsushi; Hanamoto, Katsumi; Taguchi, Takehito; Yamaoka, Kiyonori

2011-07-01

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

Antinociceptive effects of radon inhalation on formalin-induced inflammatory pain in mice.

PubMed

Yamato, Keiko; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

2013-04-01

Radon therapy is clinically useful for the treatment of inflammatory diseases. The mechanisms of pain relief remain to be fully elucidated. In this study, we investigated the antinociceptive effects of radon inhalation in a mouse model of formalin-induced inflammatory pain. Immediately, after radon inhalation at a concentration of background level (ca. 19 Bq/m(3)), 1,000 or 2,000 Bq/m(3) for 24 h, 1.35 % formalin (0.5 % formaldehyde in saline, 20 μl) was subcutaneously injected into the hind paw of mice, and we measured licking response time. Radon inhalation inhibited the second phase of response in formalin test. Formalin administration induced nociception and increased tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) levels in serum and leukocyte migration in paws. Concurrently, formalin injection decreased antioxidative functions. Radon inhalation produced antinociceptive effects, i.e., lowered serum TNF-α and NO levels, and restored antioxidative functions. The results showed that radon inhalation inhibited formalin-induced inflammatory pain.

The role of nicotine content information in smokers' subjective responses to nicotine and placebo inhalers.

PubMed

Darredeau, Christine; Barrett, Sean P

2010-11-01

A growing body of evidence suggests that non-pharmacological factors may play an important role in smoking cessation outcomes using nicotine replacement therapies. This study examined the role of information about nicotine content in smokers' subjective responses to nicotine and placebo inhalers, using the four conditions of the balanced-placebo design in a mixed within/between-subjects design. Twenty-four adult smokers (12 male) completed two laboratory sessions following overnight abstinence from smoking. Participants were randomly assigned to receive either nicotine inhalers or placebo inhalers in both sessions but were told that they received a nicotine-containing inhaler in one session and a nicotine-free inhaler in the other. In each session participants completed subjective assessments before and after inhaler administration using visual analogue scales and the Brief Questionnaire of Smoking Urges. While neither nicotine content nor information about it significantly affected cigarette craving associated with withdrawal relief, participants reported a greater reduction in craving associated with intention to smoke when told the inhalers contained nicotine than when told the inhalers were nicotine-free, regardless of actual nicotine content. Findings suggest that psychological factors play an important role in smokers' subjective responses to nicotine inhalers, the effects of which cannot be solely attributed to the direct pharmacological effects of nicotine. Copyright © 2011 John Wiley & Sons, Ltd.

Clinical perspectives on pulmonary systemic and macromolecular delivery.

PubMed

Scheuch, Gerhard; Kohlhaeufl, Martin J; Brand, Peter; Siekmeier, Ruediger

2006-10-31

The large epithelial surface area, the high organ vascularization, the thin nature of the alveolar epithelium and the immense capacity for solute exchange are factors that led the lung to serve as an ideal administration route for the application of drugs for treatment of systemic disorders. However, the deposition behaviour of aerosol particles in the respiratory tract depends on a number of physical (e.g. properties of the particle), chemical (e.g. properties of the drug) and physiological (e.g. breathing pattern, pulmonary diseases) factors. If these are not considered, it will not be possible to deposit a reproducible and sufficient amount of drug in a predefined lung region by means of aerosol inhalation. The lack of consideration of such issues led to many problems in inhalation drug therapy for many years mainly because physiological background of aerosol inhalation was not fully understood. However, over the last 20 years, there has been considerable progress in aerosol research and in the understanding of the underlying mechanisms of particle inhalation and pulmonary particle deposition. As a consequence, an increasing number of studies have been performed for the lung administration of drugs using a variety of different inhalation techniques. This review describes the physical and in part some of the physiological requirements that need to be considered for the optimization of pulmonary drug delivery to target certain lung regions.

Inhaled Treprostinil-Prodrug Lipid Nanoparticle Formulations Provide Long-Acting Pulmonary Vasodilation.

PubMed

Leifer, Franziska G; Konicek, Donna M; Chen, Kuan-Ju; Plaunt, Adam J; Salvail, Dany; Laurent, Charles E; Corboz, Michel R; Li, Zhili; Chapman, Richard W; Perkins, Walter R; S Malinin, Vladimir

2018-05-23

Treprostinil (TRE), a prostanoid analogue approved in the USA for the treatment of pulmonary arterial hypertension, requires continuous infusion or multiple dosing sessions per day for inhaled and oral routes of administration due to its short half-life. The inhaled drug is known to induce adverse systemic and local effects including headache, nausea, cough, and throat irritation which may be due at least in part to transiently high drug concentrations in the lungs and plasma immediately following administration [1]. To ameliorate these side effects and reduce dosing frequency we designed an inhaled slow-release TRE formulation. TRE was chemically modified to be an alkyl prodrug (TPD) which was then packaged into a lipid nanoparticle (LNP) carrier. Preclinical screening in a rat model of hypoxia-induced pulmonary vasoconstriction led to selection of a 16-carbon alkyl ester derivative of TRE. The TPD-LNP demonstrated approximately 10-fold lower TRE plasma C max compared to inhaled TRE solution while maintaining an extended vasodilatory effect. The favorable PK profile is attributed to gradual dissociation of TPD from the LNP and subsequent conversion to TRE. Together, this sustained presentation of TRE to the lungs and plasma is consistent with a once- or twice-daily dosing schedule in the absence of high C max -associated adverse events which could provide patients with an improved treprostinil therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Risk analysis for worker exposure to benzene

NASA Astrophysics Data System (ADS)

Hallenbeck, William H.; Flowers, Roxanne E.

1992-05-01

Cancer risk factors (characterized by route, dose, dose rate per kilogram, fraction of lifetime exposed, species, and sex) were derived for workers exposed to benzene via inhalation or ingestion. Exposure at the current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) and at leaking underground storage tank (LUST) sites were evaluated. At the current PEL of 1 ppm, the theoretical lifetime excess risk of cancer from benzene inhalation is ten per 1000. The theoretical lifetime excess risk for worker inhalation exposure at LUST sites ranged from 10 to 40 per 1000. These results indicate that personal protection should be required. The theoretical lifetime excess risk due to soil ingestion is five to seven orders of magnitude less than the inhalation risks.

Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats.

PubMed

Take, Makoto; Takeuchi, Tetsuya; Haresaku, Mitsuru; Matsumoto, Michiharu; Nagano, Kasuke; Yamamoto, Seigo; Takamura-Enya, Takeji; Fukushima, Shoji

2014-01-01

The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents.

30 CFR 71.700 - Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors. 71.700 Section 71.700 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND...

30 CFR 71.700 - Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors. 71.700 Section 71.700 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND...

30 CFR 71.700 - Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors. 71.700 Section 71.700 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-SURFACE COAL MINES AND SURFACE WORK AREAS OF UNDERGROUND...

Whole-body distribution of americium in rats for different pathways of intake.

PubMed

Doyle-Eisele, Melanie; Weber, Waylon; Melo, Dunstana R; Guilmette, Raymond A

2014-11-01

Abstract Purpose: To compare data on the whole-body distribution of americium-241 ((241)Am) in rats following intravenous injection (IV), inhalation, and wound (intramuscular injection, IM). Following exposure, each rat was placed in an individual metabolism cages for the duration of the study, 28 days (d). Urine and feces were collected daily. Tissues and organs were collected and measured. Liver and skeleton were the main sites of deposition for all routes of exposure but the content differed substantially. By 28 d, (241)Am content in liver was similar for IV and IM administrations (12 ± 4% and 14 ± 5%, respectively), which was 3-fold higher compared to inhalation. Americium-241 content in skeleton was 27% by the end of the IV study; which was 50% higher compared to the IM study and 6-fold higher compared to inhalation. The cumulative excretion in 28 d was 54% for IV (44% by feces and 10% by urine); 38% for IM (34% by feces and 4% by urine); and 84% for inhalation (83% by feces and 1% by urine). Unperturbed rat models for the three routes of administration are the baseline for evaluating the efficacy of chelating agents.

Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

PubMed

Duez, C; Gras-Masse, H; Hammad, H; Akoum, H; Didierlaurent, A; André, C; Tonnel, A B; Pestel, J

2001-01-01

We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.

Caffeine Induces a Stimulant Effect and Increases Dopamine Release in the Nucleus Accumbens Shell Through the Pulmonary Inhalation Route of Administration in Rats.

PubMed

Galvalisi, Martín; Prieto, José Pedro; Martínez, Marcela; Abin-Carriquiry, Juan Andrés; Scorza, Cecilia

2017-01-01

Oral, intraperitoneal, or intravenous have been the common routes of administration used to study the behavioral and neurochemical pharmacology of caffeine, one of the most widely used psychoactive substances worldwide. We have reported that caffeine is an active adulterant frequently found in coca-paste (CP)-seized samples, a highly addictive form of smokable cocaine. The role of caffeine in the psychostimulant and neurochemical effects induced by CP remains under study. No preclinical animal studies have been performed so far to characterize the effects of caffeine when it is administered through the pulmonary inhalation route. Caffeine (10, 25, and 50 mg) was volatilized and rats were exposed to one inhalation session of its vapor. The stimulant effect was automatically recorded and plasmatic levels of caffeine were measured. Caffeine capability (50 mg) to increase extracellular dopamine (DA) levels in nucleus accumbens shell was also studied by in vivo microdialysis in non-anesthetized animals. A dose-dependent stimulant effect induced by volatilized caffeine was observed and this effect was directly related with caffeine plasmatic levels. A significant increase in the extracellular DA was achieved after 50 mg of volatilized caffeine exposure. This is the first report showing pharmacological acute effects of caffeine through the pulmonary inhalation route of administration and suggests that this could be a condition under which caffeine can elevate its weak reinforcing effect and even enhance the psychostimulant effect and abuse liability of smokable adulterated psychostimulant drugs.

Smoke inhalation injury in a pregnant patient: a literature review of the evidence and current best practices in the setting of a classic case.

PubMed

Roderique, Ensign Joseph D; Gebre-Giorgis, Abel A; Stewart, Dane H; Feldman, Michael J; Pozez, Andrea L

2012-01-01

For smoke inhalation injury of a pregnant woman, one must treat two patients and be aware of the potential effects of carbon monoxide (CO) and cyanide (CN) poisoning on both the mother and the fetus. In a pregnant woman, the size and age of the fetus and the degree of poisoning allow for tremendous variability in the toxicity of CO and CN and their respective treatment options. The authors will review a case of a 32-year-old woman who was at 37 weeks of gestation and admitted to the Evans-Haynes Burn Center after a house fire and received hydroxocobalamin (Cyanokit) for suspected CN poisoning. In addition, a review of the literature, current guidelines, and treatment options of inhalation injury during pregnancy will be discussed. The authors will focus only on the toxic components of smoke inhalation injury rather than the mechanical components from heat and particulate damage. Literature review clearly identifies that the treatment of pregnant women with inhalation injury remains a controversial subject. The use of hydroxocobalamin (Cyanokit) as a treatment modality for potential CN poisoning in a pregnant patient has not been reported in the literature. Animal studies have shown that combined CO and CN poisoning are more lethal than either one alone and at lower concentrations. Due to the synergistic effects of CO and CN, and because these two toxins concentrate at even higher levels in the fetus than the mother, the authors will clarify the urgent seriousness of prompt administration of hydroxocobalamin in a pregnant patient with suspected smoke inhalation injury. This case review details the treatment of a 32-year-old woman who was at 36 weeks of gestation on admission to the Evans-Haynes Burn Center. The authors will report her injuries and the course of treatment. Although burned and presenting with concomitant smoke inhalation injury, both the woman and her child fared well with no significant complications due to the smoke inhalation at 6 months of follow-up. Smoke inhaled from modern structural fires potentially contains both CN and CO gases. This makes the prompt recognition of this injury and selection of appropriate therapy an emergent priority. In October 2010, the Food and Drug Administration approved hydroxocobalamin for use in pregnant patients in the acute setting when CN toxicity is suspected. Because CO and CN have additive effects when both are present in the body, the prompt administration of hydroxocobalamin not only eliminates the effects of CN but also potentially attenuates its synergistic effects on CO. It is only through a better understanding of the details of smoke inhalation injury, the current treatment options, and the considerations regarding their use that new research and strong guidelines can be developed to better serve our patients.

Inhalable particulate drug delivery systems for lung cancer therapy: Nanoparticles, microparticles, nanocomposites and nanoaggregates.

PubMed

Abdelaziz, Hadeer M; Gaber, Mohamed; Abd-Elwakil, Mahmoud M; Mabrouk, Moustafa T; Elgohary, Mayada M; Kamel, Nayra M; Kabary, Dalia M; Freag, May S; Samaha, Magda W; Mortada, Sana M; Elkhodairy, Kadria A; Fang, Jia-You; Elzoghby, Ahmed O

2018-01-10

There is progressive evolution in the use of inhalable drug delivery systems (DDSs) for lung cancer therapy. The inhalation route offers many advantages, being non-invasive method of drug administration as well as localized delivery of anti-cancer drugs to tumor tissue. This article reviews various inhalable colloidal systems studied for tumor-targeted drug delivery including polymeric, lipid, hybrid and inorganic nanocarriers. The active targeting approaches for enhanced delivery of nanocarriers to lung cancer cells were illustrated. This article also reviews the recent advances of inhalable microparticle-based drug delivery systems for lung cancer therapy including bioresponsive, large porous, solid lipid and drug-complex microparticles. The possible strategies to improve the aerosolization behavior and maintain the critical physicochemical parameters for efficient delivery of drugs deep into lungs were also discussed. Therefore, a strong emphasis is placed on the approaches which combine the merits of both nanocarriers and microparticles including inhalable nanocomposites and nanoaggregates and on the optimization of such formulations using the proper techniques and carriers. Finally, the toxicological behavior and market potential of the inhalable anti-cancer drug delivery systems are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats

PubMed Central

2018-01-01

Background Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. Methods This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. Results In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. Conclusions Acquired N2O hyperthermia in rats is remarkably robust, and occurs even despite the availability of ambient temperatures that might fully counter the hyperthermia. Increased locomotion in the gradient may contribute to hyperthermia. Our data are consistent with an allostatic dis-coordination of autonomic and behavioral thermoregulatory mechanisms during drug administration. Our results have implications for research on N2O abuse as well as research on the role of allostasis in drug addiction. PMID:29672605

Infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses.

PubMed

Yamashita, Kazuto; Muir, William W; Tsubakishita, Sae; Abrahamsen, Eric; Lerch, Phillip; Izumisawa, Yasuharu; Kotani, Tadao

2002-10-15

To evaluate effects of infusion of guaifenesin, ketamine, and medetomidine in combination with inhalation of sevoflurane versus inhalation of sevoflurane alone for anesthesia of horses. Randomized clinical trial. 40 horses. Horses were premedicated with xylazine and anesthetized with diazepam and ketamine. Anesthesia was maintained by infusion of guaifenesin, ketamine, and medetomidine and inhalation of sevoflurane (20 horses) or by inhalation of sevoflurane (20 horses). A surgical plane of anesthesia was maintained by controlling the inhaled concentration of sevoflurane. Sodium pentothal was administered as necessary to prevent movement in response to surgical stimulation. Hypotension was treated with dobutamine; hypoxemia and hypercarbia were treated with intermittent positive-pressure ventilation. The quality of anesthetic induction, maintenance, and recovery and the quality of the transition to inhalation anesthesia were scored. The delivered concentration of sevoflurane (ie, the vaporizer dial setting) was significantly lower and the quality of transition to inhalation anesthesia and of anesthetic maintenance were significantly better in horses that received the guaifenesin-ketamine-medetomidine infusion than in horses that did not. Five horses, all of which received sevoflurane alone, required administration of pentothal. Recovery time and quality of recovery were not significantly different between groups, but horses that received the guaifenesin-ketamine-medetomidine infusion required fewer attempts to stand. Results suggest that in horses, the combination of a guaifenesin-ketamine-medetomidine infusion and inhalation of sevoflurane resulted in better transition and maintenance phases while improving cardiovascular function and reducing the number of attempts needed to stand after the completion of anesthesia, compared with inhalation of sevoflurane.

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment

PubMed Central

Gordon, Sarah E; Cartwright, Neil; Griffiths, Mark J D

2009-01-01

AIMS Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100–400 µg) or sublingual nitroglycerin (NTG; 25–400 µg). RESULTS For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 ± 0.41 and 3.66 ± 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100–400 µg) did not cause a significant change in RI. CONCLUSIONS In healthy volunteers the RI response to inhaled salbutamol (100–200 µg) averaged over 5–15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 µg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication. PMID:19843066

Different effects of propofol and isoflurane on cochlear blood flow and hearing function in Guinea pigs.

PubMed

Xiao, Ying; Wen, Jian; Bai, Yanxia; Duan, Na; Jing, G X

2014-01-01

To investigate the effects of isoflurane and propofol on mean arterial pressure (MAP), cochlear blood flow (CoBF), distortion-product otoacoustic emission (DPOAE), and the ultrastructure of outer hair cells (OHCs) in guinea pig cochleae. Forty-eight male guinea pigs were randomly assigned to one of six treatment groups. Groups 1 to 3 were infused (i.v.) with a loading dose of propofol (5 mg/kg) for 5 min and three maintenance doses (10, 20, or 40 mg kg-1·h-1, respectively) for 115 min. Groups 4 to 6 were inhaled with isoflurane at concentrations of 1.15 vol%, 2.30 vol% or 3.45 vol% respectively for 120 min. CoBF and MAP were recorded prior to and at 5 min intervals during drug administration. DPOAE was measured before, immediately after, and 1 h after administration. Following the final DPOAE test, cochleae were examined using scanning electron microscopy. Propofol treatment reduced MAP in a dose-dependent manner. CoBF and DPOAE showed increases at propofol maintenance doses of 10 and 20 mg kg-1·h-1. Inhalation of isoflurane at concentrations of 2.30 vol% and 3.45 vol% reduced MAP and CoBF. DPOAE amplitude increased following inhalation of 1.15 vol% isoflurane, but decreased following inhalations of 2.30 vol% and 3.45 vol%. Cochlear structure was changed following inhalation of either 2.30 vol% or 3.45 vol% isoflurane. Propofol could decrease MAP and increase both CoBF and DPOAE without affecting OHC structure. Inhalation of isoflurane at concentrations >2.30 vol% decreased CoBF and DPOAE, and produced injury to OHCs.

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

The pharmacology of chymotrypsin administered by inhalation

PubMed Central

Golberg, L.; Martin, L. E.; Sheard, P.; Harrison, C.

1960-01-01

The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [131I]. Quantitative measurements of the absorption and distribution of inhaled chymotrypsin- [131I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [131I] subsequently detached from it. The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm. ImagesFIG. 2FIG. 3 PMID:13850540

Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

PubMed Central

Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice. PMID:23213269

Pediatric cyanide poisoning by fire smoke inhalation: a European expert consensus. Toxicology Surveillance System of the Intoxications Working Group of the Spanish Society of Paediatric Emergencies.

PubMed

Mintegi, Santiago; Clerigue, Nuria; Tipo, Vincenzo; Ponticiello, Eduardo; Lonati, Davide; Burillo-Putze, Guillermo; Delvau, Nicolas; Anseeuw, Kurt

2013-11-01

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

Inhibitory effects of pretreatment with radon on acute alcohol-induced hepatopathy in mice.

PubMed

Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

2012-01-01

We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

Treatment of proctalgia fugax with salbutamol inhalation.

PubMed

Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G

1996-04-01

Although no generally effective treatment for proctalgia fugax is known, inhalation of salbutamol has been reported to shorten pain attacks in isolated cases. We conducted a randomized, double-blind, placebo-controlled, crossover trial of inhaled salbutamol in 18 patients with proctalgia fugax. The clinical effect was evaluated by recording the duration of severe pain and discomfort during acute attacks. In addition, anorectal motility recordings were analyzed for possible changes in anal resting tone, sphincter relaxation during rectal distension and in rectal compliance prior to and following administration of the two test substances. Sixteen patients completed all investigations. Compared to placebo, salbutamol inhalation shortened the duration of severe pain (p = 0.019). The effect was most marked in patients having prolonged attacks. In the asymptomatic state, neither salbutamol nor placebo led to a significant change in anal resting pressure, anal relaxation during rectal distension, or rectal compliance. Salbutamol also did not alter the threshold for rectal sensation. Salbutamol inhalation shortens attacks of severe pain in patients with proctalgia fugax. The mechanism of this effect remains unexplained.

The effect of inhaled K+ channel openers on bronchoconstriction and airway microvascular leakage in anaesthetised guinea pigs.

PubMed

Kidney, J C; Lotvall, J O; Lei, Y; Chung, K F; Barnes, P J

1996-01-18

Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaesthetised guinea pigs. We have also investigated whether inhaled HOE 234 inhibits the bronchoconstriction and plasma exudation induced by vagus nerve stimulation, which is due to the release of tachykinins from sensory nerves. Lung resistance was measured by airway resistance (RL) computed from airway and transpulmonary pressures and plasma exudation by measurement of Evans blue dye extravasation. Inhaled levcromakalim (25 mu g/ml) had a short duration of action, being effective against histamine-induced bronchoconstriction 2 min after pretreatment, but not at 10 min. Inhaled HOE 234 (25 mu g/ml) was similarly effective against histamine-induced bronchoconstriction but had a longer duration of action. Inhaled levcromakalim partially attenuated histamine-induced plasma extravasation in small airways, but not in the trachea or main bronchi, whereas inhaled HOE 234 had no effect. HOE 234 protected against non-adrenergic non-cholinergic nerve-induced bronchoconstriction, but had no effect on neurogenic- or substance P-induced plasma extravasation in the airway. Inhaled K+ channel openers protect against induced bronchoconstriction, but provide little or no protection against plasma exudation, possibly because of an increase in airway blood flow. In addition, inhaled HOE 234 had no effect on neurogenic leakage, suggesting that its vagal inhibitory effect on bronchoconstriction was on airway smooth muscle, rather than on release of neuropeptides from sensory nerves.

Cerebrovascular, cardiovascular and strength responses to acute ammonia inhalation.

PubMed

Perry, Blake G; Pritchard, Hayden J; Barnes, Matthew J

2016-03-01

Ammonia is used as a stimulant in strength based sports to increase arousal and offset fatigue however little is known about its physiological and performance effects. The purpose of this study was twofold (1) establish the physiological response to acute ammonia inhalation (2) determine whether the timing of the physiological response corresponds with a performance enhancement, if any. Fifteen healthy males completed two trials. Trial one investigated the beat-to-beat middle cerebral artery blood flow velocity (MCAv), heart rate (HR) and mean arterial pressure (MAP) response to ammonia inhalation. During trial two, participants performed a maximal single mid-thigh pull (MTP) at various time points following ammonia inhalation in a randomised order: MTPs were conducted immediately, 15, 30 and 60 s following ammonia inhalation. A MTP with no ammonia inhalation served as the control. During this trial maximal MTP force, rate of force development (RFD) and electromyography (EMG) activity were recorded. MCAvmean increased and peaked on average by 6 cm s(-1) (P < 0.001), 9.4 ± 5.5 s following ammonia inhalation. Similarly, HR was increased by 6 ± 11 beats per minute 15 s following ammonia inhalation (P < 0.001). MAP remained unchanged following inhalation (P = 0.51). The use and timing of ammonia inhalation had no effect on maximal force, RFD or EMG (all P > 0.2) compared to control. MCAv was elevated despite no increase in MAP occurring; this is indicative of a cerebrovascular vasodilation. Despite the marked cerebrovascular and cardiovascular response to ammonia inhalation no ergogenic effect was observed during the MTP, irrespective of the timing of administration.

The effects of nicotine, denicotinized tobacco, and nicotine-containing tobacco on cigarette craving, withdrawal, and self-administration in male and female smokers.

PubMed

Barrett, Sean P

2010-03-01

The effects of the acute administration of nicotine [through nicotine inhalers (NI) and placebo inhalers (PI)], nicotine-containing tobacco (NT), and denicotinized tobacco (DT), on smokers' subjective responses and motivation to smoke were examined in 22 smokers (12 male, 10 female; 11 low dependent, 11 high dependent). During four randomized blinded sessions, participants self-administered NI, PI, NT, or DT, and assessed their effects using Visual Analogue Scales and the Brief Questionnaire of Smoking Urges. They could then self-administer their preferred brand of cigarettes using a progressive ratio task. NT and DT were each associated with increased satisfaction and relaxation as well as decreased craving relative to the inhalers and NT increased ratings of stimulation relative to each of the other products. Both NT and DT delayed the onset of preferred tobacco self-administration relative to NI and PI but only NT reduced the total amount self-administered. Sex differences were evident in the effects of DT on withdrawal-related cravings with women experiencing greater DT-induced craving relief than men. Findings suggest that DT is effective in acutely reducing many smoking abstinence symptoms, especially in women, but a combination of nicotine and non-nicotine tobacco ingredients may be necessary to suppress smoking behavior.

Evidence of the rapid protective effect of formoterol dry-powder inhalation against exercise-induced bronchospasm in athletes with asthma.

PubMed

Ferrari, M; Balestreri, F; Baratieri, S; Biasin, C; Oldani, V; Lo Cascio, V

2000-01-01

Although formoterol, a new long-acting beta(2)-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. The protective effect of a formoterol (12 microg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV(1) after exercise being 29.3 +/- 14.3% and 22.9 +/- 13. 7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV(1) after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV(1) after formoterol was 5.9+/-7.2% at 15 min (p < 0.0001), and 5.8 +/- 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration. Copyright 2000 S. Karger AG, Basel

Optimization and Dose Estimation of Aerosol Delivery to Non-Human Primates.

PubMed

MacLoughlin, Ronan J; van Amerongen, Geert; Fink, James B; Janssens, Hettie M; Duprex, W Paul; de Swart, Rik L

2016-06-01

In pre-clinical animal studies, the uniformity of dosing across subjects and routes of administration is a crucial requirement. In preparation for a study in which aerosolized live-attenuated measles virus vaccine was administered to cynomolgus monkeys (Macaca fascicularis) by inhalation, we assessed the percentage of a nebulized dose inhaled under varying conditions. Drug delivery varies with breathing parameters. Therefore we determined macaque breathing patterns (tidal volume, breathing frequency, and inspiratory to expiratory (I:E) ratio) across a range of 3.3-6.5 kg body weight, using a pediatric pneumotachometer interfaced either with an endotracheal tube or a facemask. Subsequently, these breathing patterns were reproduced using a breathing simulator attached to a filter to collect the inhaled dose. Albuterol was nebulized using a vibrating mesh nebulizer and the percentage inhaled dose was determined by extraction of drug from the filter and subsequent quantification. Tidal volumes ranged from 24 to 46 mL, breathing frequencies from 19 to 31 breaths per minute and I:E ratios from 0.7 to 1.6. A small pediatric resuscitation mask was identified as the best fitting interface between animal and pneumotachometer. The average efficiency of inhaled dose delivery was 32.1% (standard deviation 7.5, range 24%-48%), with variation in tidal volumes as the most important determinant. Studies in non-human primates aimed at comparing aerosol delivery with other routes of administration should take both the inter-subject variation and relatively low efficiency of delivery to these low body weight mammals into account.

Feasibility of aerosol drug delivery to sleeping infants: a prospective observational study.

PubMed

Amirav, Israel; Newhouse, Michael T; Luder, Anthony; Halamish, Asaf; Omar, Hamza; Gorenberg, Miguel

2014-03-26

Delivery of inhaled medications to infants is usually very demanding and is often associated with crying and mask rejection. It has been suggested that aerosol administration during sleep may be an attractive alternative. Previous studies in sleeping children were disappointing as most of the children awoke and rejected the treatment. The SootherMask (SM) is a new, gentle and innovative approach for delivering inhaled medication to infants and toddlers. The present pilot study describes the feasibility of administering inhaled medications during sleep using the SM. Prospective observational study. Out patients. 13 sleeping infants with recurrent wheezing who regularly used pacifiers and were <12 months old. Participants inhaled technetium99mDTPA-labelled normal saline aerosol delivered via a Respimat Soft Mist Inhaler (SMI) (Boehringer-Ingelheim, Germany) and SM + InspiraChamber (IC; InspiRx Inc, New Jersey, USA). The two major outcomes were the acceptability of the treatment and the lung deposition (per cent of emitted dose). All infants who fulfilled the inclusion criteria successfully received the SM treatment during sleep without difficulty. Mean lung deposition (±SD) averaged 1.6±0.5% in the right lung. This study demonstrated that the combination of Respimat, IC and SM was able to administer aerosol therapy to all the sleeping infants who were regular pacifier users with good lung deposition. Administration of aerosols during sleep is advantageous since all the sleeping children accepted the mask and ensuing aerosol therapy under these conditions, in contrast to previous studies in which there was frequent mask rejection using currently available devices. NCT01120938.

Desensitization to inhaled aztreonam lysine in an allergic patient with cystic fibrosis using a novel approach.

PubMed

Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny

2012-10-01

To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to ensure that they can continue to receive these medications safely.

Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats.

PubMed

Javadi-Paydar, Mehrak; Nguyen, Jacques D; Kerr, Tony M; Grant, Yanabel; Vandewater, Sophia A; Cole, Maury; Taffe, Michael A

2018-06-16

Previous studies report sex differences in some, but not all, responses to cannabinoids in rats. The majority of studies use parenteral injection; however, most human use is via smoke inhalation and, increasingly, vapor inhalation. To compare thermoregulatory and locomotor responses to inhaled ∆ 9 -tetrahydrocannabinol (THC), cannabidiol (CBD), and their combination using an e-cigarette-based model in male and female rats METHODS: Male and female Wistar rats were implanted with radiotelemetry devices for the assessment of body temperature and locomotor activity. Animals were then exposed to THC or CBD vapor using a propylene glycol (PG) vehicle. THC dose was adjusted via the concentration in the vehicle (12.5-200 mg/mL) and the CBD (100, 400 mg/mL) dose was also adjusted by varying the inhalation duration (10-40 min). Anti-nociception was evaluated using a tail-withdrawal assay following vapor inhalation. Plasma samples obtained following inhalation in different groups of rats were compared for THC content. THC inhalation reduced body temperature and increased tail-withdrawal latency in both sexes equivalently and in a concentration-dependent manner. Female temperature, activity, and tail-withdrawal responses to THC did not differ between estrus and diestrus. CBD inhalation alone induced modest hypothermia and suppressed locomotor activity in both males and females. Co-administration of THC with CBD, in a 1:4 ratio, significantly decreased temperature and activity in an approximately additive manner and to similar extent in each sex. Plasma THC varied with the concentration in the PG vehicle but did not differ across rat sex. In summary, the inhalation of THC or CBD, alone and in combination, produces approximately equivalent effects in male and female rats. This confirms the efficacy of the e-cigarette-based method of THC delivery in female rats.

Toxic leucoencephalopathy after 'chasing the dragon'.

PubMed

Singh, Rajinder; Saini, Monica

2015-06-01

Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

Bronchospasm and anaphylactic shock following lidocaine aerosol inhalation in a patient with butane inhalation lung injury.

PubMed

Lee, Min-Young; Park, Kyong Ah; Yeo, So-Jeong; Kim, Shin-Hee; Goong, Hyeun-Jeong; Jang, An-Soo; Park, Choon-Sik

2011-10-01

Allergic reactions to local anesthetics are very rare and represent <1% of all adverse local anesthetics reactions. A 54-year-old man was admitted to the hospital in the winter because of shortness of breath. The patient reportedly had an inhalation lung injury due to butane gas fuel. On the fifth day, he developed an asthmatic attack and anaphylactic shock immediately after lidocaine aerosol administration to prepare for bronchoscopy to confirm an acute inhalational lung injury diagnosis. Cardiopulmonary resuscitation was performed immediately after respiratory arrest, and the patient was admitted to the intensive care unit intubated and on a ventilator. He was extubated safely on the third post-cardiopulmonary resuscitation day. These observations suggest that aerosol lidocaine anesthesia may cause airway narrowing and anaphylactic shock. Practitioners should be aware of this potential complication. We report on this case with a brief review of the literature.

Comparison of peak inspiratory flow rate via the Breezhaler®, Ellipta® and HandiHaler® dry powder inhalers in patients with moderate to very severe COPD: a randomized cross-over trial.

PubMed

Altman, Pablo; Wehbe, Luis; Dederichs, Juergen; Guerin, Tadhg; Ament, Brian; Moronta, Miguel Cardenas; Pino, Andrea Valeria; Goyal, Pankaj

2018-06-14

The chronic and progressive nature of chronic obstructive pulmonary disease (COPD) requires self-administration of inhaled medication. Dry powder inhalers (DPIs) are increasingly being used for inhalation therapy in COPD. Important considerations when selecting DPIs include inhalation effort required and flow rates achieved by patients. Here, we present the comparison of the peak inspiratory flow rate (PIF) values achieved by COPD patients, with moderate to very severe airflow limitation, through the Breezhaler®, the Ellipta® and the HandiHaler® inhalers. The effects of disease severity, age and gender on PIF rate were also evaluated. This randomized, open-label, multicenter, cross-over, Phase IV study recruited patients with moderate to very severe airflow limitation (Global Initiative for Obstructive Lung Disease 2014 strategy), aged ≥40 years and having a smoking history of ≥10 pack years. No active drug or placebo was administered during the study. The inhalation profiles were recorded using inhalers fitted with a pressure tap and transducer at the wall of the mouthpiece. For each patient, the inhalation with the highest PIF value, out of three replicate inhalations per device, was selected for analysis. A paired t-test was performed to compare mean PIFs between each combination of devices. In total, 97 COPD patients were enrolled and completed the study. The highest mean PIF value (L/min ± SE) was observed with the Breezhaler® (108 ± 23), followed by the Ellipta® (78 ± 15) and the HandiHaler® (49 ± 9) inhalers and the lowest mean pressure drop values were recorded with the Breezhaler® inhaler, followed by the Ellipta® inhaler and the HandiHaler® inhaler, in the overall patient population. A similar trend was consistently observed in patients across all subgroups of COPD severity, within all age groups and for both genders. Patients with COPD were able to inhale with the least inspiratory effort and generate the highest mean PIF value through the Breezhaler® inhaler when compared with the Ellipta® and the HandiHaler® inhalers. These results were similar irrespective of patients' COPD severity, age or gender. The trial was registered with ClinicalTrials.gov NCT02596009 on 4 November 2015.

Comparison of three different inhalant anesthetic agents (isoflurane, sevoflurane, desflurane) in red-tailed hawks (Buteo jamaicensis).

PubMed

Granone, Tiffany D; de Francisco, Olga N; Killos, Maria B; Quandt, Jane E; Mandsager, Ron E; Graham, Lynelle F

2012-01-01

To compare isoflurane, sevoflurane and desflurane for inhalant anesthesia in red-tailed hawks (Buteo jamaicensis) in terms of the speed and characteristics of induction; cardiovascular and respiratory parameters while anesthetized; and speed and quality of recovery. Prospective, cross over, randomized experimental study. 12 healthy adult red-tailed hawks. Anesthesia was induced with isoflurane, sevoflurane or desflurane in oxygen via face mask in a crossover, randomized design with a 1 week washout period between each treatment. Hawks were tracheally intubated, allowed to breathe spontaneously, and instrumented for cardiopulmonary monitoring. Data collected included heart rate, respiratory rate, end-tidal CO(2) , inspired and expired agent, SpO(2,) temperature, systolic blood pressure, time to intubation and time to recovery (tracking). Recovery was subjectively scored on a 4 point scale as well as a summary evaluation, by a single blinded observer. No significant difference in time to induction and time to extubation was noted with the administration of isoflurane, sevoflurane or desflurane. Time to the ability of the bird to follow a moving object with its eyes (tracking) was significantly faster with the administration of sevoflurane and desflurane. All recoveries were scored 1 or 2 and were assessed as good to excellent. No significant difference was noted in heart rate, blood pressure and temperature among the three inhalants. Administration of isoflurane resulted in lower respiratory rates. Overall, although isoflurane remains the most common inhaled anesthetic in avian practice, sevoflurane and desflurane both offer faster time to tracking, while similar changes in cardiopulmonary function were observed with each agent during anesthesia of healthy red-tailed hawks. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes

PubMed Central

Lee, Changkyu; Choi, Ji Su; Kim, Insoo; Oh, Kyung Taek; Lee, Eun Seong; Park, Eun-Seok; Lee, Kang Choon; Youn, Yu Seok

2013-01-01

Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal-Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human lung epithelial cells (A549). Finally, the lung deposition characteristics and hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary administration in imprinting control region (ICR) and type 2 diabetic db/db mice. Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a diameter of ~700 nm and a positive surface charge of +28.5 mV Chitosan-coated PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal-Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs remained in the lungs for ~72 hours after pulmonary administration, whereas most non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery system for the treatment of type 2 diabetes. PMID:23976850

Preliminary experience with combined inhaled milrinone and prostacyclin in cardiac surgical patients with pulmonary hypertension.

PubMed

Laflamme, Maxime; Perrault, Louis P; Carrier, Michel; Elmi-Sarabi, Mahsa; Fortier, Annik; Denault, André Y

2015-02-01

To retrospectively evaluate the effects of combined inhaled prostacyclin and milrinone to reduce the severity of pulmonary hypertension when administered prior to cardiopulmonary bypass. Retrospective case control analysis of high-risk patients undergoing cardiac surgery. Single cardiac center. Sixty one adult cardiac surgical patients with pulmonary hypertension, 40 of whom received inhalation therapy. Inhaled milrinone and inhaled prostacyclin were administered before cardiopulmonary bypass (CPB). Administration of both inhaled prostacyclin and milrinone was associated with reductions in central venous pressure, and mean pulmonary artery pressure, increases in cardiac index, heart rate, and the mean arterial-to-mean pulmonary artery pressure ratio (p < 0.05), with no significant change in mean arterial pressure. The rate of difficult and complex separation from CPB was 51% in the inhaled group and 70% in the control group (p = 0.1638). Postoperative vasoactive requirement was reduced at 12 hours (35.9 v 73.7% p<0.01) and 24 hours (25.6 v 57.9% p<0.05) postoperatively in the combined inhaled agent group. Hospital length of stay and mortality were similar between the groups. Preemptive treatment of pulmonary hypertension with a combination of inhaled prostacyclin and milrinone before CPB was associated with a reduction in the severity of pulmonary hypertension. In addition, a significant reduction in vasoactive support in the intensive care unit during the first 24 hours after cardiac surgery was observed. The impact of this strategy on postoperative survival needs to be determined. Copyright © 2014 Elsevier Inc. All rights reserved.

75 FR 13678 - Schedules of Controlled Substances; Table of Excluded Nonnarcotic Products: Nasal Decongestant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... 1117-AB23 Schedules of Controlled Substances; Table of Excluded Nonnarcotic Products: Nasal Decongestant Inhalers Manufactured by Classic Pharmaceuticals, LLC AGENCY: Drug Enforcement Administration (DEA... Administration (DEA) is updating the Table of Excluded Nonnarcotic Products found in 21 CFR 1308.22 to include...

Pharmacokinetic and Pharmacodynamic Properties of a Novel Inhaled Insulin

PubMed Central

Heinemann, Lutz; Baughman, Robert; Boss, Anders; Hompesch, Marcus

2016-01-01

Advances in insulin treatment options over recent decades have markedly improved the management of diabetes. Despite this, glycemic control remains suboptimal in many people with diabetes. Although postprandial glucose control has been improved with the development of subcutaneously injected rapid-acting insulin analogs, currently available insulins are not able to fully mimic the physiological time–action profile of endogenously secreted insulin after a meal. The delayed onset of metabolic action and prolonged period of effect induce the risk of postprandial hyperglycemia and late postprandial hypoglycemia. A number of alternative routes of insulin administration have been investigated over time in an attempt to overcome the limitations associated with subcutaneous administration and to provide an improved time–action insulin profile more closely simulating physiological prandial insulin release. Among these, pulmonary insulin delivery has shown the most promise. Technosphere® Inhaled Insulin (TI) is a rapid-acting inhaled human insulin recently approved by the FDA for prandial insulin therapy. In this article we discuss the pharmacokinetic and pharmacodynamic properties of TI, and, based on key studies performed during its clinical development, the implications for improved postprandial glucose control. PMID:27378794

Patient preferences for medicine administration for acute agitation: results from an internet-based survey of patients diagnosed with bipolar disorder or schizophrenia in two Nordic countries.

PubMed

Jørgensen, Tine Rikke; Emborg, Charlotte; Dahlen, Karianne; Bøgelund, Mette; Carlborg, Andreas

2018-01-01

The objective was to elicit patient preferences for medicine administration method in the management of acute agitation episodes among patients diagnosed with bipolar disorder or schizophrenia. The patients' experiences of acute agitation episodes and their management of episodes were also explored. Data were collected via an anonymous, internet-based survey of residents in Denmark or Sweden with schizophrenia or bipolar disorder (October 2014 to December 2014). Inclusion criteria were having a diagnosis of schizophrenia or bipolar disorder, and being above 18 years of age. The questionnaire included questions about preferences for medication attributes, experiences with pharmacological treatment for agitation and involvement in treatment plans. A total of 237 diagnosed patients (61 with schizophrenia; 176 with bipolar disorder) completed the questionnaire. Agitation episodes were experienced by 90% of the respondents. In total, 83% of the respondents reported having received treatment with tablets. When patients were presented with the attributes of an inhalation method, respondents stated that the fast onset of action, low risk of adverse reactions and least invasive form of drug delivery were positive attributes of treatment with inhalation. Inhalation is a new delivery route for treatment of acute agitation in patients diagnosed with bipolar disorder or schizophrenia. Inhalation is the preferred treatment method for acute agitation among Danish and Swedish patients with bipolar disorder or schizophrenia.

Inhaled Antibiotics for Gram-Negative Respiratory Infections

PubMed Central

Fraidenburg, Dustin R.; Scardina, Tonya

2016-01-01

SUMMARY Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

Effectiveness of Ginger Essential Oil on Postoperative Nausea and Vomiting in Abdominal Surgery Patients.

PubMed

Lee, Yu Ri; Shin, Hye Sook

2017-03-01

The purpose of this study was to examine the effectiveness of aromatherapy with ginger essential oil on nausea and vomiting in abdominal surgery patients. This was a quasi-experimental study with a nonequivalent control group and repeated measures. The experimental group (n = 30) received ginger essential oil inhalation. The placebo control group (n = 30) received normal saline inhalation. The level of postoperative nausea and vomiting was measured using a Korean version of the Index of Nausea, Vomiting, and Retching (INVR) at baseline and at 6, 12, and 24 h after aromatherapy administration. The data were collected from July 23 to August 22, 2012. Nausea and vomiting scores were significantly lower in the experimental group with ginger essential oil inhalation than those in the placebo control group with normal saline. In the experimental group, the nausea and vomiting scores decreased considerably in the first 6 h after inhaled aromatherapy with ginger essential oil. Findings indicate that ginger essential oil inhalation has implications for alleviating postoperative nausea and vomiting in abdominal surgery patients.

Dust exposure in workers from grain storage facilities in Costa Rica.

PubMed

Rodríguez-Zamora, María G; Medina-Escobar, Lourdes; Mora, Glend; Zock, Jan-Paul; van Wendel de Joode, Berna; Mora, Ana M

2017-08-01

About 12 million workers are involved in the production of basic grains in Central America. However, few studies in the region have examined the occupational factors associated with inhalable dust exposure. (i) To assess the exposure to inhalable dust in workers from rice, maize, and wheat storage facilities in Costa Rica; (ii) to examine the occupational factors associated with this exposure; and (iii) to measure concentrations of respirable and thoracic particles in different areas of the storage facilities. We measured inhalable (<100μm) dust concentrations in 176 personal samples collected from 136 workers of eight grain storage facilities in Costa Rica. We also measured respirable (<4μm) and thoracic (<10μm) dust particles in several areas of the storage facilities. Geometric mean (GM) and geometric standard deviation (GSD) inhalable dust concentrations were 2.0mg/m 3 and 7.8 (range=<0.2-275.4mg/m 3 ). Personal inhalable dust concentrations were associated with job category [GM for category/GM for administrative staff and other workers (95% CI)=4.4 (2.6, 7.2) for packing; 20.4 (12.3, 34.7) for dehulling; 109.6 (50.1, 234.4) for unloading in flat bed sheds; 24.0 (14.5, 39.8) for unloading in pits; and 31.6 (18.6, 52.5) for drying], and cleaning task [15.8 (95% CI: 10.0, 26.3) in workers who cleaned in addition to their regular tasks]. Higher area concentrations of thoracic dust particles were found in wheat (GM and GSD=4.3mg/m 3 and 4.5) and maize (3.0mg/m 3 and 3.9) storage facilities, and in grain drying (2.3mg/m 3 and 3.1) and unloading (1.5mg/m 3 and 4.8) areas. Operators of grain storage facilities showed elevated inhalable dust concentrations, mostly above international exposure limits. Better engineering and administrative controls are needed. Copyright © 2017 Elsevier GmbH. All rights reserved.

Inhaled budesonide for the prevention of bronchopulmonary dysplasia.

PubMed

Bassler, Dirk

2017-10-01

Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system of infants with evolving or established bronchopulmonary dysplasia (BPD) with a lower risk of undesirable side effects compared to systemic corticosteroids. However, before deciding whether to use inhaled corticosteroids for BPD in routine clinical practice, the available randomized study data need to be considered. Currently published systematic reviews from the Cochrane Collaboration conclude that there is no role for inhaled corticosteroids in neither prevention nor treatment of BPD outside clinical trials. In contrast multiple observational studies indicate that a large number of preterm infants in Europe, North America and East Asia receive inhaled corticosteroids for this indication in routine clinical care. This discrepancy between evidence and practice prompted a large randomized controlled trial (RCT) investigating the role of inhaled budesonide for the prevention of BPD which was recently published and showed a significant reduction in the incidence of BPD. However, the primary outcome (a composite of death or BPD at 36 weeks postmenstrual age) was only of borderline significance as a result of a non-significant trend to increased mortality in the budesonide group. Results of the long-term follow up from this study should be considered when defining the future role of inhaled corticosteroids for BPD. Additionally, updated systematic reviews will help to determine whether the observed mortality difference between the two comparison groups represents truth or artifact.

Performance of dry powder inhalers with single dosed capsules in preschool children and adults using improved upper airway models.

PubMed

Lindert, Sandra; Below, Antje; Breitkreutz, Joerg

2014-02-06

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

Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration.

PubMed

Sumner, Susan C J; Janszen, Derek B; Asgharian, Bahman; Moore, Timothy A; Parkinson, Horace D; Fennell, Timothy R

2003-01-01

Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce emissions. Understanding the metabolism and distribution of TAME is needed to assess potential human health issues. The effect of dose level, duration of exposure and route of administration on the metabolism and distribution of TAME were investigated in male and female F344 rats and CD-1 mice following inhalation or gavage administration. By 48 h after exposure, >96% of the administered radioactivity was expired in air (16-71%) or eliminated in urine and feces (28-72%). Following inhalation exposure, mice had a two- to threefold greater relative uptake of [14C]TAME compared with rats. Metabolites were excreted in urine of rats and mice that are formed by glucuronide conjugation of tertiary amyl alcohol (TAA), oxidation of TAA to 2,3-dihydroxy-2-methylbutane and glucuronide conjugation of 2,3-dihydroxy-2-methylbutane. A saturation in the uptake and metabolism of TAME with increased exposure concentration was indicated by a decreased relative uptake of total [14C]TAME equivalents and an increase in the percentage expired as volatiles. A saturation of P-450 oxidation of TAA was indicated by a disproportional decrease of 2,3-dihydroxy-2-methylbutane and its glucuronide conjugate with increased exposure concentration. Copyright 2003 John Wiley & Sons, Ltd.

An overview of animal models for assessing synthetic vitreous fibers (SVFs) safety.

PubMed

Johnson, N F

1994-12-01

Synthetic vitreous fibers (SVFs) are materials with many important commercial applications. The fibrous nature of the SVFs raises concerns about their potential human health hazards. However, sufficient epidemiological data do not exist to establish the hazardous nature of all SVFs. In addition, the cellular and molecular mechanisms underlying the induction of pulmonary lesions are only partially understood. Without sufficient evidence to associate fiber exposure and lung disease, animal bioassays have been used to identify specific hazardous fibers. These bioassays include inhalation exposures, intratracheal instillation, and intracavitary injection (intrapleural and intraperitoneal). Inhalation exposures of animals most closely represent the human experience, but these exposures are costly and time-consuming to conduct. Intratracheal and intracavitary administrations of fiber are alternatives to inhalation exposures; however, they do not represent human exposures and can give false positive results. The limitations of the noninhalation approaches must be considered when addressing the potential for a respirable fiber to induce human lung disease. In addition, when the results from inhalation exposures do not agree with the alternative animal assays, most weight should be given to the animal inhalation assays because of the limitations of the alternative approaches. To determine the safety of SVFs, both the inhalation and noninhalation approaches are suggested.

Kuwaiti oil fires—Particulate monitoring

NASA Astrophysics Data System (ADS)

Husain, Tahir; Amin, Mohamed B.

The total suspended particulate (TSP) matters using a high-volume sampler and inhalable particulate matters using PM-10 samplers were collected at various locations in the Eastern Province of Saudi Arabia during and after the Kuwaiti oil fires. The collected samples were analysed for toxic metals and oil hydrocarbon concentrations including some carcinogenic organic compounds in addition to gravimetric analysis. The concentration values of particulate matters were determined on a daily basis at Dhahran. Abqaiq, Rahima, Tanajib and Jubail locations. The analyses of the filters show a high concentration of the inhalable particulate at various locations, especially when north or northwest winds were blowing. It was found that the inhalable particulate concentration exceeded the Meteorology and Environmental Protection Administration (MEPA) permissible limit of 340 μg m- 3 at most of these locations during May-October 1991. A trend between the total suspended particulate and inhalable particulate measured concurrently at the same locations was observed and a regression equation was developed to correlate PM-10 data with the total suspended particulate data.

Adenosine receptor subtypes in the airways responses to 5'-adenosine monophosphate inhalation of sensitized guinea-pigs.

PubMed

Smith, N; Broadley, K J

2008-09-01

Endogenous adenosine levels are raised in the lungs during asthma attacks. 5'-adenosine monophosphate (5'-AMP) inhalation in asthmatics causes bronchoconstriction and in sensitized guinea-pigs induces early (EAR) and late asthmatic responses (LAR), airway hyper-reactivity (AHR) and inflammatory cell recruitment to the lungs. The aim of this study was to investigate the roles of A(1), A(2A), A(2B) and A(3) adenosine receptors in these responses to inhaled 5'-AMP in sensitized guinea-pigs. Comparisons were made with the effect of dexamethasone treatment on 5'-AMP-induced responses. Functional airways responses to inhaled 5'-AMP (3 and 300 mM) of actively sensitized, conscious guinea-pigs were determined by whole-body plethysmography following administration of selective adenosine receptor antagonists or their vehicles. AHR to inhaled histamine (1 mM) and inflammatory cell influx in bronchoalveolar lavage fluid were determined. 5'-AMP at 3 mM caused an immediate bronchoconstriction (EAR), whereas 300 mM caused bronchodilatation. Both responses were followed at 6 h by a LAR, together with inflammatory cell influx and AHR to histamine. The A(2A) receptor antagonist, ZM241385, further enhanced cell influx after 5'-AMP inhalation (3 and 300 mM), and blocked the immediate bronchodilator response to 300 mM 5'-AMP, exposing an EAR. The A(2B) receptor antagonist, MRS1706 (in the presence of ZM241385), inhibited the LAR, AHR and cell influx, following inhalation of 5'-AMP (300 mM). The A(3) receptor antagonist, MRS1220, inhibited 5'-AMP-induced inflammatory cell influx. The A(1) receptor antagonist, DPCPX (in the presence of ZM241385), inhibited the EAR following 5'-AMP inhalation (300 mM). Dexamethasone inhibited the LAR, AHR and cell influx following inhalation of 5'-AMP (300 mM). All four adenosine receptor subtypes play various roles in the airways responses to inhaled 5'-AMP in sensitized guinea-pigs.

The imidazobenzodiazepine Ro 15-4513 antagonizes methoxyflurane anesthesia.

PubMed

Moody, E J; Skolnick, P

1988-01-01

Parenteral administration of the imidazobenzodiazepine Ro 15-4513 (a high affinity ligand of the benzodiazepine receptor with partial inverse agonist qualities) produced a dose dependent reduction in sleep time of mice exposed to the inhalation anesthetic, methoxyflurane. The reductions in methoxyflurane sleep time ranged from approximately 20% at 4 mg/kg to approximately 38% at 32 mg/kg of Ro 15-4513. Co-administration of the benzodiazepine receptor antagonist Ro 15-1788 (16 mg/kg) or the inverse agonists DMCM (5-20 mg/kg) and FG 7142 (22.5 mg/kg) blocks this effect which suggests that the reductions in methoxyflurane sleep time produced by Ro 15-4513 are mediated via occupation of benzodiazepine receptors. Moreover, neither DMCM (5-20 mg/kg) nor FG 7142 (22.5 mg/kg) reduced methoxyflurane sleep time which suggests this effect of Ro 15-4513 cannot be attributed solely to its partial inverse agonist properties. These observations support recent findings that inhalation anesthetics may produce their depressant effects via perturbation of the benzodiazepine/GABA receptor chloride channel complex, and suggest that Ro 15-4513 may serve as a prototype of agents capable of antagonizing the depressant effects of inhalation anesthetics such as methoxyflurane.

Dry powder antibiotic aerosol product development: inhaled therapy for tuberculosis.

PubMed

Hickey, Anthony J; Misra, Amit; Fourie, P Bernard

2013-11-01

Inhaled therapies offer a unique approach to the treatment of tuberculosis (TB) using a relevant target organ system as a route of administration. The number of research reports on this topic has been increasing exponentially in the last decade but studies of clinical efficacy have been rare in recent times. The challenge is to take many research findings and translate them into a strategy for product development. Dry powder inhalers are the dominant drug product under consideration by those interested in the inhaled therapy for TB. A range of factors including candidate drug, formulation, device selection, drug product testing for proof of concept, and preclinical and clinical purposes all demand different considerations. The following review is intended to raise awareness of a growing body of evidence, suggesting that inhaled therapy for TB is possible and desirable. In addition, it is intended to outline key elements of the product-development activity for this particular application that has not been discussed elsewhere in the literature. Hopefully, this will encourage those with development expertise to seriously contemplate the steps required to bring such products forward. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Inhaled Antibiotics for Gram-Negative Respiratory Infections.

PubMed

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

2016-07-01

Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effect of inhaled and systemic glucocorticoid treatment on CD4+ regulatory and effector T cells in a mouse model of allergic asthma.

PubMed

Zuśka-Prot, Monika; Maślanka, Tomasz

2017-04-01

To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4 + T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4 + effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4 + Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4 + Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4 + Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4 + T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Competence in metered dose inhaler technique among community pharmacy professionals in Gondar town, Northwest Ethiopia: Knowledge and skill gap analysis.

PubMed

Belachew, Sewunet Admasu; Tilahun, Fasil; Ketsela, Tirsit; Achaw Ayele, Asnakew; Kassie Netere, Adeladlew; Getnet Mersha, Amanual; Befekadu Abebe, Tamrat; Melaku Gebresillassie, Begashaw; Getachew Tegegn, Henok; Asfaw Erku, Daniel

2017-01-01

When compared to systemic administration, if used correctly inhalers deliver a smaller enough percent of the drug right to the site of action in the lungs, with a faster onset of effect and with reduced systemic availability that minimizes adverse effects. However, the health professionals' and patients' use of metered dose inhaler is poor. This study was aimed to explore community pharmacy professionals' (pharmacists' and druggists') competency on metered dose inhaler (MDI) technique. A cross sectional study was employed on pharmacy professionals working in community drug retail outlets in Gondar town, northwest Ethiopia from March to May 2017. Evaluation tool was originally taken and adapted from the National Asthma Education and Prevention Programmes of America (NAEPP) step criteria for the demonstration of a metered dose inhaler to score the knowledge/proficiency of using the inhaler. Among 70 community pharmacy professionals approached, 62 (32 pharmacists and 30 druggists/Pharmacy technicians) completed the survey with a response rate of 85.6%. Only three (4.8%) respondents were competent by demonstrating the vital steps correctly. Overall, only 13 participants got score seven or above, but most of them had missed the essential steps which included steps 1, 2, 5, 6, 7 or 8. There was a significant difference (P = 0.015) in competency of demonstrating adequate inhalational technique among respondents who took training on basic inhalational techniques and who did not. This study shown that, community pharmacy professionals' competency of MDI technique was very poor. So as to better incorporate community pharmacies into future asthma illness management and optimize the contribution of pharmacists, interventions would emphasis to improve the total competence of community pharmacy professionals through establishing and providing regular educational programs.

Which inhaled corticosteroid and long-acting β-agonist combination is better in patients with moderate-to-severe asthma, a dry powder inhaler or a pressurized metered-dose inhaler?

PubMed

Muraki, Masato; Gose, Kyuya; Hanada, Soichiro; Sawaguchi, Hirochiyo; Tohda, Yuji

2017-11-01

Two main types of devices are used to facilitate the administration of inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) in combination, dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). There are few reports comparing the effects of the two devices, and it is unknown which should be recommended for asthma patients with given sets of characteristics. In the current study, the beneficial effects and side effects associated with DPIs and pMDIs were compared, and the question of which device should be recommended for asthma patients was investigated. A prospective, randomized, crossover, comparative study in adult outpatients with asthma was conducted using salmeterol/fluticasone propionate combination (SFC) 50 μg/250 μg, one inhalation of Adoair ® 250 Diskus ® twice daily or two inhalations of Adoair ® 125 Aerosol twice daily, for 8 weeks. Questionnaires, exhaled nitric oxide (FeNO) tests and pulmonary function tests were administered after the use of each device for 8 weeks, and the results derived from each device were compared. Sixty-eight subjects were included in the final analysis. There were no significant differences between quality-of-life scores, FeNO, spirometry test results and forced oscillation results. With regard to patient preferences, 57.4% preferred the Adoair ® Aerosol and 35.3% preferred the Adoair ® Diskus ® , as determined via the comparative evaluation questionnaire. Although DPI prescription accounts for the predominant market share of combined ICS/LABA in Japan, patients preferred a pMDI device to a DPI device. Compared to DPIs, pMDIs may be the preferential choice for patients with asthma.

Orally Administered DTPA Di-ethyl Ester for Decorporation of 241Am in dogs: Assessment of Safety and Efficacy in an Inhalation-Contamination Model

PubMed Central

Huckle, James E.; Sadgrove, Matthew P.; Pacyniak, Erik; Leed, Marina G. D.; Weber, Waylon M.; Doyle-Eisele, Melanie; Guilmette, Raymond A.; Agha, Bushra J.; Susick, Robert L.; Mumper, Russell J.; Jay, Michael

2016-01-01

Purpose Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA) approved for decorporation of 241Am, however, an oral product is considered more amenable in a mass casualty situation. The diethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination. Materials and methods Single dose decorporation efficacy of C2E2 administered 24-hours post contamination was determined in beagle dogs using a 241Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test. Results Oral administration of C2E2 significantly increased 241Am elimination over untreated controls and significantly reduced the retention of 241Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic. Conclusions The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of 241Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies. PMID:25912343

Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice.

PubMed

Manaenko, Anatol; Lekic, Tim; Ma, Qingyi; Zhang, John H; Tang, Jiping

2013-05-01

Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to antioxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage. Controlled in vivo laboratory study. Animal research laboratory. One hundred seventy-one 8-week-old male CD-1 mice were used. Collagenase-induced intracerebral hemorrhage model in 8-week-old male CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier permeability and neurologic deficits were investigated at 24 and 72 hours after intracerebral hemorrhage. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model intracerebral hemorrhage. At 24 and 72 hours post intracerebral hemorrhage, animals showed blood-brain barrier disruption, brain edema, and neurologic deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated blood-brain barrier disruption, and improved neurobehavioral function. Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.

Hydrogen inhalation ameliorated mast cell mediated brain injury after ICH in mice

PubMed Central

Manaenko, Anatol; Lekic, Tim; Ma, Qingyi; Zhang, John H.; Tang, Jiping

2012-01-01

OBJECTIVE Hydrogen inhalation was neuroprotective in several brain injury models. Its mechanisms are believed to be related to anti-oxidative stress. We investigated the potential neurovascular protective effect of hydrogen inhalation especially effect on mast cell activation in a mouse model of intracerebral hemorrhage (ICH). DESIGN Controlled in vivo laboratory study. SETTING Animal research laboratory SUBJECTS 171, 8 weeks old male CD-1 mice were used. INTERVENTIONS Collagenase-induced ICH model in 8 weeks old, male, CD-1 mice was used. Hydrogen was administrated via spontaneous inhalation. The blood-brain barrier (BBB) permeability and neurological deficits were investigated at 24 and 72 hours after ICH. Mast cell activation was evaluated by Western blot and immuno-staining. The effects of hydrogen inhalation on mast cell activation were confirmed in an autologous blood injection model ICH. MEASURMENT AND MAIN RESULTS At 24 and 72 hours post-ICH, animals showed BBB disruption, brain edema, neurological deficits, accompanied with phosphorylation of Lyn kinase and release of tryptase, indicating mast cell activation. Hydrogen treatment diminished phosphorylation of Lyn kinase and release of tryptase, decreased accumulation and degranulation of mast cells, attenuated BBB disruption and improved neurobehavioral function. CONCLUSION Activation of mast cells following ICH contributed to increase of BBB permeability and brain edema. Hydrogen inhalation preserved BBB disruption by prevention of mast cell activation after ICH. PMID:23388512

Dramatic response to inhaled dobesilate in a patient with lung squamous cell cancer

PubMed Central

Cuevas, Pedro; Sueiro, Antonio; Navío, Pilar; Giménez-Gallego, Guillermo

2012-01-01

The effectiveness of local application, by inhalation, of dobesilate, an inhibitor of fibroblast growth factor signalling, in a patient with squamous cell lung carcinoma is reported. To our knowledge, these are the first published data on the efficacy of dobesilate in the treatment of this disease. The antimitotic, antiangiogenic, proapoptotic and anti-inflammatory activities of dobesilate can be important factors to consider, in explaining the efficacy of the treatment. Dobesilate administration can be a therapeutic option in patients with lung cancer having poor performance status or severe complications. PMID:22952275

The efficacies of pure LICAM(C) and DTPA for enhancing the elimination of plutonium-238 and americium-241 from rats after their inhalation as nitrate.

PubMed

Stradling, G N; Stather, J W; Gray, S A; Moody, J C; Ellender, M; Hodgson, A

1989-01-01

After the inhalation of 238Pu and 241Am as nitrate, the repeated administration of DTPA is far superior to that of LICAM(C) for enhancing their elimination from the body. The therapeutic efficacies of these chelating agents are however similar after intravenous injection of 238Pu as citrate. It is concluded that DTPA should remain the agent of choice for treating persons contaminated internally with transportable forms of these actinides.

Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

PubMed Central

Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

2014-01-01

Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen. PMID:24975958

Anesthetic drugs and onset of malignant hyperthermia.

PubMed

Visoiu, Mihaela; Young, Michael C; Wieland, Keith; Brandom, Barbara W

2014-02-01

The time between the beginning of anesthetic administration and recognition of the first sign of malignant hyperthermia (MH) (MH onset time) could differ among anesthetic drugs. We examined the time of the first signs of suspected MH, anesthetic drugs administered, subject age, and year of event in Adverse Metabolic/Musculoskeletal Reaction to Anesthesia reports in the North American Malignant Hyperthermia Registry. Inclusion criteria were judgment by the reporting clinician that the event was possible or fulminant MH, documentation of the time when anesthetic administration began, and the time when the first MH sign was noted. Descriptive statistics, Kruskal-Wallis analysis, and nonparametric correlation were used to assess the difference in MH onset times under different conditions. Four hundred seventy-seven cases met inclusion criteria; 58.5% were possible MH and 41.5% fulminant MH. Inhaled anesthetic and succinylcholine were given in 53.9% of cases, inhaled anesthetic only in 41.7%, and succinylcholine without inhaled anesthetics in 2.9%. No causative anesthetic drugs were reported in 7 MH cases. In 394 patients exposed to only 1 of the 4 inhaled anesthetics, without regard for subject age, MH onset time was shorter in the presence of halothane than any of the other anesthetics and shorter after succinylcholine in all anesthetics. If succinylcholine was not given, MH onset was shorter during sevoflurane anesthesia than during desflurane or isoflurane. In 322 cases, 1 rather than multiple first signs of MH were reported with masseter spasm as the earliest MH sign. In 339 cases in which masseter spasm was not reported, there was no difference in MH onset time with or without succinylcholine. In 146 cases in which masseter spasm was not reported and succinylcholine was not given, MH onset was shorter during halothane anesthesia, than during exposure to desflurane, or isoflurane. MH onset time during sevoflurane was shorter than during desflurane or isoflurane. MH was reported later in the course of anesthesia after 1998, when halothane and succinylcholine were less often reported. MH occurred after succinylcholine administration in the absence of inhaled anesthetics. We could not separate an effect of age from that of other variables. The onset of MH has been observed later during desflurane and isoflurane anesthesia than during exposure to sevoflurane. Since 1998, MH signs have more often appeared later, in the second or third hour of anesthesia, than they did before 1998.

Instillation versus Inhalation of Multiwalled Carbon Nanotubes: Exposure-Related Health Effects, Clearance, and the Role of Particle Characteristics

PubMed Central

2015-01-01

Inhaled multiwalled carbon nanotubes (MWCNTs) may cause adverse pulmonary responses due to their nanoscale, fibrous morphology and/or biopersistance. This study tested multiple factors (dose, time, physicochemical characteristics, and administration method) shown to affect MWCNT toxicity with the hypothesis that these factors will influence significantly different responses upon MWCNT exposure. The study is unique in that (1) multiple administration methods were tested using particles from the same stock; (2) bulk MWCNT formulations had few differences (metal content, surface area/functionalization); and (3) MWCNT retention was quantified using a specialized approach for measuring unlabeled MWCNTs in rodent lungs. Male Sprague–Dawley rats were exposed to original (O), purified (P), and carboxylic acid functionalized (F) MWCNTs via intratracheal instillation and inhalation. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected at postexposure days 1 and 21 for quantifying biological responses and MWCNTs in lung tissues by programmed thermal analysis. At day 1, MWCNT instillation produced significant BALF neutrophilia and MWCNT-positive macrophages. Instilled O- and P-MWCNTs produced significant inflammation in lung tissues, which resolved by day 21 despite MWCNT retention. MWCNT inhalation produced no BALF neutrophilia and no significant histopathology past day 1. However, on days 1 and 21 postinhalation of nebulized MWCNTs, significantly increased numbers of MWCNT-positive macrophages were observed in BALF. Results suggest (1) MWCNTs produce transient inflammation if any despite persistence in the lungs; (2) instilled O-MWCNTs cause more inflammation than P- or F-MWCNTs; and (3) MWCNT suspension media produce strikingly different effects on physicochemical particle characteristics and pulmonary responses. PMID:25144856

Inhalative nanomedicine--opportunities and challenges.

PubMed

Bur, Michael; Henning, Andreas; Hein, Stephanie; Schneider, Marc; Lehr, Claus-Michael

2009-07-01

Inhalation therapy is still limited by the low bioavailability of the administered drugs. Advantages of the pulmonary administration site like large resorption area, low enzymatic equipment, and circumvention of the first pass effect are set into perspective by the rigid barrier properties of the alveolar region. As a consequence, the systemic bioavailability of peptides and proteins is still relatively limited, even when administered by modern pharmaceutical aerosol technologies. In the context of advanced pulmonary drug therapy the use of nanoparticles as alternative to micronsized drug formulation could be of special interest, because nanoparticles seem to overcome some cellular barriers quite efficiently. Besides such outstanding permeation properties, nanoparticles may also hold promises to escape from pulmonary clearance mechanisms and to allow for cell-specific targeting within the lung. Such opportunities and challenges of inhalative nanomedicine are reviewed in this short review.

Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery

PubMed Central

Sinsuebpol, Chutima; Chatchawalsaisin, Jittima; Kulvanich, Poj

2013-01-01

Purpose The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with mannitol and investigate pulmonary absorption in rats. Methods The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. Results sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. Conclusion The sCT-CS-NPs with mannitol based spray dried powders were prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation. PMID:24039397

Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery.

PubMed

Sinsuebpol, Chutima; Chatchawalsaisin, Jittima; Kulvanich, Poj

2013-01-01

The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with mannitol and investigate pulmonary absorption in rats. The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. The sCT-CS-NPs with mannitol based spray dried powders were prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation.

Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-κB signaling pathway

PubMed Central

ZHANG, CHAO-BIN; TANG, YI-CHEN; XU, XUE-JUN; GUO, SHI-XIANG; WANG, HUAI-ZHI

2015-01-01

Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The present study was designed to investigate the effect of hydrogen inhalation on liver ischemia/reperfusion (I/R) injury in rats. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min. This was followed by reperfusion for 180 min. The rats subsequently underwent syngeneic orthotopic liver transplantation. Inhalation of various concentrations (1, 2 and 3%) of hydrogen gas and its administration for different durations (1, 3 and 6 h) immediately prior to the I/R injury allowed the optimal dose and duration of administration to be determined. Liver injury was evaluated through biochemical and histopathological examinations. The expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, were measured by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction (qPCR). Liver nuclear factor κB (NF-κB) was detected by qPCR and western blot analysis. Inhalation of hydrogen gas at 2% concentration for 1 h significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the expression of cytokines, including IL-6, TNF-α, early growth response protein 1 (Egr-1) and IL-1β, and morphological damage. In addition, the mRNA and protein expression levels of NF-κB, heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2) and zinc finger protein A20 (A20) in rats where only the donors received hydrogen were significantly increased compared with those in rats where both the donor and recipient, or only the recipient received hydrogen. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF-κB signaling pathway. PMID:26136944

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.

Inhaled nano- and microparticles for drug delivery

PubMed Central

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

2015-01-01

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

Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function.

PubMed

Cabanes, L; Costes, F; Weber, S; Regnard, J; Benvenuti, C; Castaigne, A; Guerin, F; Lockhart, A

1992-06-18

Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double-blind, crossover design. In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long-term benefit in patients with heart failure will require further study.

Inhaled Beta Agonist Bronchodilator Does Not Affect Trans-diaphragmatic Pressure Gradient but Decreases Lower Esophageal Sphincter Retention Pressure in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Gastroesophageal Reflux Disease (GERD).

PubMed

Del Grande, Leonardo M; Herbella, Fernando A M; Bigatao, Amilcar M; Jardim, Jose R; Patti, Marco G

2016-10-01

Chronic obstructive pulmonary disease (COPD) patients have a high incidence of gastroesophageal reflux disease (GERD) whose pathophysiology seems to be linked to an increased trans-diaphragmatic pressure gradient and not to a defective esophagogastric barrier. Inhaled beta agonist bronchodilators are a common therapy used by patients with COPD. This drug knowingly not only leads to a decrease in the lower esophageal sphincter (LES) resting pressure, favoring GERD, but also may improve ventilatory parameters, therefore preventing GERD. This study aims to evaluate the effect of inhaled beta agonist bronchodilators on the trans-diaphragmatic pressure gradient and the esophagogastric barrier. We studied 21 patients (mean age 67 years, 57 % males) with COPD and GERD. All patients underwent high-resolution manometry and esophageal pH monitoring. Abdominal and thoracic pressure, trans-diaphragmatic pressure gradient (abdominal-thoracic pressure), and the LES retention pressure (LES basal pressure-transdiaphragmatic gradient) were measured before and 5 min after inhaling beta agonist bronchodilators. The administration of inhaled beta agonist bronchodilators leads to the following: (a) a simultaneous increase in abdominal and thoracic pressure not affecting the trans-diaphragmatic pressure gradient and (b) a decrease in the LES resting pressure with a reduction of the LES retention pressure. In conclusion, inhaled beta agonist bronchodilators not only increase the thoracic pressure but also lead to an increased abdominal pressure favoring GERD by affecting the esophagogastric barrier.

Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice

PubMed Central

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

2017-01-01

ABSTRACT Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury. PMID:28498931

[Patient compliance with inhaled medication approach in community pharmacy].

PubMed

Maesschalck, J; Duquet, N

2012-03-01

Non compliance with chronic administration of inhaled medication is a great pitfall. Pharmacists have an important task in optimizing patient compliance since they hold several advantages for that purpose: they possess an overview of the patient's medication, even prescription free medication such as cough medicines. Moreover, the pharmacist is capable of explaining the role of the medication in therapy and he enjoys the patient's confidence to do so. This article highlights some strategies to measure patient compliance and seeks to understand the underlying reasons for non-compliance. The appropriate pharmacist's action will depend on that reason.

Health Manpower in Missouri.

ERIC Educational Resources Information Center

Harmon, Loyd M., Ed.

This supplementary report begins with general information on licensing boards, associations, societies, reliability of data, and similar items. The second, and main, section deals with the following disciplines: administrators, doctors of medicine, doctors of osteopathy, dentists, dental hygienists, dieticians, inhalation therapists, medical…

Inhalation therapy in mechanical ventilation

PubMed Central

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

2015-01-01

Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients. PMID:26578139

The Rationale and Evidence for Use of Inhaled Antibiotics to Control Pseudomonas aeruginosa Infection in Non-cystic Fibrosis Bronchiectasis

PubMed Central

2018-01-01

Abstract Non-cystic fibrosis bronchiectasis (NCFBE) is a chronic inflammatory lung disease characterized by irreversible dilation of the bronchi, symptoms of persistent cough and expectoration, and recurrent infective exacerbations. The prevalence of NCFBE is on the increase in the United States and Europe, but no licensed therapies are currently available for its treatment. Although there are many similarities between NCFBE and cystic fibrosis (CF) in terms of respiratory symptoms, airway microbiology, and disease progression, there are key differences, for example, in response to treatment, suggesting differences in pathogenesis. This review discusses possible reasons underlying differences in response to inhaled antibiotics in people with CF and NCFBE. Pseudomonas aeruginosa infections are associated with the most severe forms of bronchiectasis. Suboptimal levels of antibiotics in the lung increase the mutation frequency of P. aeruginosa and lead to the development of mucoid strains characterized by formation of a protective polysaccharide biofilm. Mucoid strains of P. aeruginosa are associated with a chronic infection stage, requiring long-term antibiotic therapy. Inhaled antibiotics provide targeted delivery to the lung with minimal systemic toxicity and adverse events compared with oral/intravenous routes of administration, and they could be alternative treatment options to help address some of the treatment challenges in the management of severe cases of NCFBE. This review provides an overview of completed and ongoing trials that evaluated inhaled antibiotic therapy for NCFBE. Recently, several investigators conducted phase 3 randomized controlled trials with inhaled aztreonam and ciprofloxacin in patients with NCFBE. While the aztreonam trial results were not associated with significant clinical benefit in NCFBE, initial results reported from the inhaled ciprofloxacin (dry powder for inhalation and liposome-encapsulated/dual-release formulations) trials hold promise. A more targeted approach could identify specific populations of NCFBE patients who benefit from inhaled antibiotics. PMID:29077527

Methamphetamine and Amphetamine Isomer Concentrations in Human Urine Following Controlled Vicks VapoInhaler Administration

PubMed Central

Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; Flegel, Ron; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

2014-01-01

Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography–mass spectrometry (GC–MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC–MS method with >99% purity of R-(−)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC–MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0–1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT® II Plus, KIMS® II and DRI® had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT® II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation. PMID:25217541

Educational Programs in the Health Field.

ERIC Educational Resources Information Center

Hospitals, 1971

1971-01-01

This document lists by location educational programs in the health field in the United States and Canada. Areas covered include Certified Laboratory Assistant Programs, Cytotechnology, Dental Hygiene, Dentistry, Dietetics, Hospital Administration, Inhalation Therapy, Library Science, Medical Illustration, Medical Records, Medical Technology,…

E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

PubMed

Steinberg, Michael B; Zimmermann, Mia Hanos; Delnevo, Cristine D; Lewis, M Jane; Shukla, Parth; Coups, Elliot J; Foulds, Jonathan

2014-11-01

Novel nicotine delivery products, such as electronic cigarettes (e-cigarettes), have dramatically grown in popularity despite limited data on safety and benefit. In contrast, the similar U.S. Food and Drug Administration (FDA)-approved nicotine inhaler is rarely utilized by smokers. Understanding this paradox could be helpful to determine the potential for e-cigarettes as an alternative to tobacco smoking. To compare the e-cigarette with the nicotine inhaler in terms of perceived benefits, harms, appeal, and role in assisting with smoking cessation. A cross-over trial was conducted from 2012 to 2013 PARTICIPANTS/INTERVENTIONS: Forty-one current smokers age 18 and older used the e-cigarette and nicotine inhaler each for 3 days, in random order, with a washout period in between. Thirty-eight participants provided data on product use, perceptions, and experiences. The Modified Cigarette Evaluation Questionnaire (mCEQ) measured satisfaction, reward, and aversion. Subjects were also asked about each product's helpfulness, similarity to cigarettes, acceptability, image, and effectiveness in quitting smoking. Cigarette use was also recorded during the product-use periods. The e-cigarette had a higher total satisfaction score (13.9 vs. 6.8 [p < 0.001]; range for responses 3-21) and higher reward score (15.8 vs. 8.7 [p < 0.001]; range for responses 5-35) than the inhaler. The e-cigarette received higher ratings for helpfulness, acceptability, and "coolness." More subjects would use the e-cigarette to make a quit attempt (76 %) than the inhaler (24 %) (p < 0.001). Eighteen percent (7/38) of subjects abstained from smoking during the 3-day periods using the e-cigarette vs. 10 % (4/38) using the inhaler (p = 0.18). The e-cigarette was more acceptable, provided more satisfaction, and had higher perceived benefit than the inhaler during this trial. E-cigarettes have the potential to be important nicotine delivery products owing to their high acceptance and perceived benefit, but more data are needed to evaluate their actual efficacy and safety. Providers should be aware of these issues, as patients will increasingly inquire about them.

Systemic delivery of parathyroid hormone (1-34) using inhalation dry powders in rats.

PubMed

Codrons, Valérie; Vanderbist, Francis; Verbeeck, Roger K; Arras, Mohammed; Lison, Dominique; Préat, Véronique; Vanbever, Rita

2003-05-01

The aim of this work was to prepare and characterize inhalation dry powders of human parathyroid hormone (PTH), as well as to assess their efficacy for systemic delivery of the peptide and safety in rats. The powders were prepared by spray-drying using PTH, sugars, dipalmitoylphosphatidylcholine, and/or albumin. They presented an average primary particle diameter of 4.5 microm and tap density of 0.06 g/cm(3), a mass median aerodynamic diameter between 3.9 and 5.9 microm, and reached up to 98% emitted dose and up to 61% fine particle fraction in the multi-stage liquid impinger using a Spinhaler inhaler device. Varying the airflow rate from 30 to 100 L/min had limited influence on the aerodynamic behavior of the aerosols. The absolute PTH bioavailability was 21% after intratracheal administration of the powder formed of PTH/albumin/lactose/dipalmitoylphosphatidylcholine and 18% after subcutaneous injection in rats. Equilibrium dialysis revealed a 78% binding of PTH to albumin and the withdrawal of albumin from the powder increased absolute bioavailability after inhalation from 21 to 34%. No acute inflammation appeared in the lung up to 48 h after a single inhalation. The increased bioavailability of the optimized powder aerosol of PTH makes it a promising alternative to subcutaneous injection. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:938-950, 2003

Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

PubMed Central

Wu, Xiao; Zhang, Weifen; Hayes, Don; Mansour, Heidi M

2013-01-01

In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug – cyclosporine A – for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters. PMID:23569375

Effect of the pulmonary deposition and in vitro permeability on the prediction of plasma levels of inhaled budesonide formulation.

PubMed

Salar-Behzadi, Sharareh; Wu, Shengqian; Mercuri, Annalisa; Meindl, Claudia; Stranzinger, Sandra; Fröhlich, Eleonore

2017-10-30

The growing interest in the inhalable pharmaceutical products requires advanced approaches to safe and fast product development, such as in silico tools that can be used for estimating the bioavailability and toxicity of developed formulation. GastroPlus™ is one of the few available software packages for in silico simulation of PBPK profile of inhalable products. It contains a complementary module for calculating the lung deposition, the permeability and the systemic absorption of inhalable products. Experimental values of lung deposition and permeability can also be used. This study aims to assess the efficiency of simulation by applying experimental permeability and deposition values, using budesonide as a model substance. The lung deposition values were obtained from the literature, the lung permeability data were experimentally determined by culturing Calu-3 cells under air-liquid interface and submersed conditions to morphologically resemble bronchial and alveolar epithelial cells, respectively. A two-compartment PK model was created for i.v. administration and used as a background for the in silico simulation of the plasma profile of budesonide after inhalation. The predicted plasma profile was compared with the in vivo data from the literature and the effects of experimental lung deposition and permeability on prediction were assessed. The developed model was significantly improved by using realistic lung deposition data combined with experimental data for peripheral permeability. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-06-01

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

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

PubMed

Hostrup, M; Jessen, S; Onslev, J; Clausen, T; Porsbjerg, C

2017-07-01

While chronic systemic administration of glucocorticoids increases muscle Na + ,K + ATPase content, such effect is unexplored after therapeutic inhalation. We investigated the effect of therapeutic inhalation of the glucocorticoid budesonide on Na + ,K + ATPase content of skeletal muscle in men. Ten healthy trained subjects, aged 23 ± 4 years (mean ± 95% CI), participated in the study. Before and after 2 weeks of daily inhalation of budesonide (1.6 mg/day), a biopsy was taken from the vastus lateralis muscle for measurement of Na + ,K + ATPase content and blood samples were drawn for determination of plasma budesonide, cortisol, and K + . Subjects' performance during cycling to fatigue at 90% of incremental peak power output (iPPO) was measured in response to 4 mg inhaled terbutaline to maximally stimulate Na + ,K + ATPase activity. Plasma concentrations of budesonide rose to 5.0 ± 1.6 nM with the intervention, whereas no changes were observed in plasma cortisol. Muscle Na + ,K + ATPase content increased (P ≤ 0.01) by 46 ± 34 pmol/(g wet wt) (17% increase) with the intervention. Cycling performance at 90% of iPPO did not change (P = 0.21) with the intervention (203 vs 214 s) in response to terbutaline. The present observations show that therapeutic inhalation of glucocorticoids increases muscle Na + ,K + ATPase content, but does not enhance high-intensity cycling endurance in response to terbutaline. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The in vitro and in vivo investigation of a novel small chamber dry powder inhalation delivery system for preclinical dosing to rats.

PubMed

Sellers, Shari; Horodnik, Walter; House, Aileen; Wylie, Jennifer; Mauser, Peter; Donovan, Brent

2015-01-01

This research describes a novel "minitower" dry powder delivery system for nose-only delivery of dry powder aerosols to spontaneously breathing rats. The minitower system forces pressurized air through pre-filled capsules to deliver aerosolized drug to four nose ports; three of which house spontaneously breathing rats, with the fourth used as a control. Within each port are vent filters which capture drug that was not inhaled for further quantitation. These vent filters along with a novel control system referred to as the "artificial rat lung", allow for the theoretical amount of drug delivered and subsequently inhaled by each rat to be calculated. In vitro and in vivo studies have demonstrated this system's ability to deliver aerosolized drug to rats. The in vitro study showed that ∼30% of the starting dose reached the 4 ports and was available for inhalation. During in-vivo studies, rats inhaled ∼34% of the delivered dose. Of the estimated inhaled dose, 12-18% was detectable in the various tissue samples, with over 30% of the recovered dose found in the rat's lungs. Results show that this system is capable of reproducibly delivering drug to the lungs of spontaneously breathing rats. Advantages over current delivery methods include being amenable to the administration of multiple doses and using less (milligram) amount of starting material. In addition, this technique avoids anesthesia which is typically required for instillation or insufflation, and thus has the potential as an efficient and noninvasive aerosol delivery method for preclinical drug development.

21 CFR 529.1455 - Methoxyflurane.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of anesthesia, and the type of equipment used. Anesthesia may be induced with methoxyflurane alone, or by the intravenous administration of a short-acting general anesthetic or by inhalation of another anesthetic agent. (2) Indications for use. For the induction and maintenance of general anesthesia. (3...

21 CFR 529.1455 - Methoxyflurane.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of anesthesia, and the type of equipment used. Anesthesia may be induced with methoxyflurane alone, or by the intravenous administration of a short-acting general anesthetic or by inhalation of another anesthetic agent. (2) Indications for use. For the induction and maintenance of general anesthesia. (3...

Anthrax: an update

PubMed Central

Kamal, SM; Rashid, AKM M; Bakar, MA; Ahad, MA

2011-01-01

Anthrax is a zoonotic disease caused by Bacillus anthracis. It is potentially fatal and highly contagious disease. Herbivores are the natural host. Human acquire the disease incidentally by contact with infected animal or animal products. In the 18th century an epidemic destroyed approximately half of the sheep in Europe. In 1900 human inhalational anthrax occured sporadically in the United States. In 1979 an outbreak of human anthrax occured in Sverdlovsk of Soviet Union. Anthrax continued to represent a world wide presence. The incidence of the disease has decreased in developed countries as a result of vaccination and improved industrial hygiene. Human anthrax clinically presents in three forms, i.e. cutaneous, gastrointestinal and inhalational. About 95% of human anthrax is cutaneous and 5% is inhalational. Gastrointestinal anthrax is very rare (less than 1%). Inhalational form is used as a biological warefare agent. Penicillin, ciprofloxacin (and other quinolones), doxicyclin, ampicillin, imipenem, clindamycin, clarithromycin, vancomycin, chloramphenicol, rifampicin are effective antimicrobials. Antimicrobial therapy for 60 days is recommended. Human anthrax vaccine is available. Administration of anti-protective antigen (PA) antibody in combination with ciprofloxacin produced 90%-100% survival. The combination of CPG-adjuvanted anthrax vaccine adsorbed (AVA) plus dalbavancin significantly improved survival. PMID:23569822

Electroencephalogram of Healthy Horses During Inhaled Anesthesia.

PubMed

Williams, D C; Aleman, M R; Brosnan, R J; Fletcher, D J; Holliday, T A; Tharp, B; Kass, P H; Steffey, E P; LeCouteur, R A

2016-01-01

Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. Six healthy horses. Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation. Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications. The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

A model for treating avian aspergillosis: serum and lung tissue kinetics for Japanese quail (Coturnix japonica) following single and multiple aerosol exposures of a nanoparticulate itraconazole suspension.

PubMed

Rundfeldt, Chris; Wyska, Elżbieta; Steckel, Hartwig; Witkowski, Andrzej; Jeżewska-Witkowska, Grażyna; Wlaź, Piotr

2013-11-01

Aspergillosis is frequently reported in parrots, falcons and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but administration requires repeated oral dosing and the safety margin is narrow. We describe lung tissue and serum pharmacokinetics of a nanoparticulate ITRA suspension administered to Japanese quail by aerosol exposure. Aerosolized ITRA (1 and 10% suspension) administered over 30 min did not induce adverse clinical reactions in quail upon single or 5-day repeated doses. High lung concentrations, well above the inhibitory levels for A. fumigatus, of 4.14 ± 0.19 μg/g and 27.5 ± 4.58 μg/g (mean ± SEM, n = 3), were achieved following single-dose inhalation of 1% and 10% suspension, respectively. Upon multiple dose administration of 10% suspension, mean lung concentrations reached 104.9 ± 10.1 μg/g. Drug clearance from the lungs was slow with terminal half-lives of 19.7 h and 35.8 h following inhalation of 1% and 10% suspension, respectively. Data suggest that lung clearance is solubility driven. Lung concentrations of hydroxy-itraconazole reached 1-2% of the ITRA lung tissue concentration indicating metabolism in lung tissue. Steady, but low, serum concentrations of ITRA could be measured after multiple dose administration, reaching less than 0.1% of the lung tissue concentration. This formulation may represent a novel, easy to administer treatment modality for fungal lung infection, preventing high systemic exposure. It may also be useful as metaphylaxis to prevent the outbreak of aspergillosis in colonized animals.

Free and Glucuronide Whole Blood Cannabinoids' Pharmacokinetics after Controlled Smoked, Vaporized, and Oral Cannabis Administration in Frequent and Occasional Cannabis Users: Identification of Recent Cannabis Intake.

PubMed

Newmeyer, Matthew N; Swortwood, Madeleine J; Barnes, Allan J; Abulseoud, Osama A; Scheidweiler, Karl B; Huestis, Marilyn A

2016-12-01

There is increasing interest in markers of recent cannabis use because following frequent cannabis intake, Δ 9 -tetrahydrocannabinol (THC) may be detected in blood for up to 30 days. The minor cannabinoids cannabidiol, cannabinol (CBN), and THC-glucuronide were previously detected for ≤2.1 h in frequent and occasional smokers' blood after cannabis smoking. Cannabigerol (CBG), Δ 9 -tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-THCV might also be recent use markers, but their blood pharmacokinetics have not been investigated. Additionally, while smoking is the most common administration route, vaporization and edibles are frequently used. We characterized blood pharmacokinetics of THC, its phase I and phase II glucuronide metabolites, and minor cannabinoids in occasional and frequent cannabis smokers for 54 (occasional) and 72 (frequent) hours after controlled smoked, vaporized, and oral cannabis administration. Few differences were observed between smoked and vaporized blood cannabinoid pharmacokinetics, while significantly greater 11-nor-9-carboxy-THC (THCCOOH) and THCCOOH-glucuronide concentrations occurred following oral cannabis. CBG and CBN were frequently identified after inhalation routes with short detection windows, but not detected following oral dosing. Implementation of a combined THC ≥5 μg/L plus THCCOOH/11-hydroxy-THC ratio <20 cutoff produced detection windows <8 h after all routes for frequent smokers; no occasional smoker was positive 1.5 h or 12 h following inhaled or oral cannabis, respectively. Vaporization and smoking provide comparable cannabinoid delivery. CBG and CBN are recent-use cannabis markers after cannabis inhalation, but their absence does not exclude recent use. Multiple, complimentary criteria should be implemented in conjunction with impairment observations to improve interpretation of cannabinoid tests. Clinicaltrials.gov Identifier: NCT02177513. © 2016 American Association for Clinical Chemistry.

Batch crystallization of rifapentine for inhalable tuberculosis medication

NASA Astrophysics Data System (ADS)

Wijanarko, Anondho; Meivita, Maria Prisca; Hermansyah, Heri; Sahlan, Muhamad; Lakerveld, Richard

2018-02-01

In the midst of Tuberculosis (TB) pandemic, a research about new tuberculosis drug that results in more rapid resolution of tubercular infection is important. It will play a crucial role in accelerating the reductions in tuberculosis incidence that is occurring worldwide. The effectiveness of rifapentine has been assessed and it has been proven to be the most effective antibiotics for TB. A frequent administration and dose of rifapentine resulted in more rapid resolution of tubercular infection. However, based on former research, high exposure levels for treatment shortening may be unachievable with oral administration and might instead be achieved by direct aerosol delivery of rifapentine to the pulmonary site of infection. Therefore, with the growing interest in the effectiveness of rifapentine in frequent administration and dose, this research integrates an inhalable form of crystalline rifapentine prepared using a batch process. Moreover, this research investigates the effect of seed loading, supersaturation ratio, and residence time on the characterization of crystalline rifapentine in order to form a crystalline rifapentine in an inhalable size. The research was carried out by using anti-solvent crystallization method with acetone as a solvent and distilled water as an anti-solvent. Based on the assessment of various operating variables, it can be concluded that the optimum result was obtained at the unseeded experiment with supersaturation ratio = 1.26. Unseeded experiments are preferred because the ideal size for therapeutic aerosol was achieved in unseeded experiments. At the request of all authors the above article is being retracted due to publication without knowledge or consent from one of the principal investigators of the research listed on the article, Dr. Richard Lakerveld. This article is retracted from the scientific record with effect from 18 May 2018.

Efficacy of bacteriophage therapy in a model of Burkholderia cenocepacia pulmonary infection

PubMed Central

Carmody, Lisa A.; Gill, Jason J.; Summer, Elizabeth J.; Sajjan, Uma S.; Gonzalez, Carlos F.; Young, Ryland F.; LiPuma, John J.

2009-01-01

The therapeutic potential of bacteriophage (phage) in a mouse model of acute B. cenocepacia pulmonary infection was assessed. Phage were administered by either intranasal (i.n.) inhalation or intraperitoneal (i.p.) injection. Bacterial density, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNFα) levels were significantly reduced in lungs of mice treated with i.p. phage. No significant differences in lung bacterial density or MIP-2 levels were found between untreated mice and mice treated with i.n. phage, i.p. UV-inactivated phage, or i.p. λ phage controls. Mock-infected mice treated with phage showed no significant increase in lung MIP-2 or TNFα levels compared to mock-infected / mock-treated mice. We have demonstrated the efficacy of phage therapy in an acute B. cenocepacia lung infection model. Systemic administration of phage was more effective than inhalational administration, suggesting that circulating phage have better access to bacteria in lung compared to topical phage. PMID:20001604

Changes in neuroactive steroid secretion associated with CO2-induced panic attacks in normal individuals.

PubMed

Brambilla, Francesca; Perini, Giulia; Serra, Mariangela; Pisu, Maria Giuseppina; Zanone, Stefano; Toffanin, Tommaso; Milleri, Stefano; Garcia, Cristina Segura; Biggio, Giovanni

2013-10-01

Neuroactive steroids modulate anxiety in experimental animals and possibly in humans. The secretion of these compounds has been found to be altered in panic disorder (PD), with such alterations having been suggested to be a possible cause or effect of panic symptomatology. Panic-like attacks can be induced in healthy individuals by administration of panicogenic agents or by physical procedures, and we have now measured the plasma concentrations of neuroactive steroids in such individuals before, during, and after panicogenic inhalation of CO2 in order to investigate whether abnormalities of neuroactive steroid secretion might contribute to the pathogenesis of PD. Fifty-nine psychologically and physically healthy subjects, including 42 women (11 in the follicular phase of the menstrual cycle, 14 in the luteal phase, and 17 taking contraceptive pills) and 17 men, who experienced a panic-like attack on previous exposure to 7% CO2 were again administered 7% CO2 for 20min. Thirty-three of these individuals (responders) again experienced a panic-like attack, whereas the remaining 26 subjects did not (nonresponders). All subjects were examined with the VAS-A and PSL-III-R scales for anxiety and panic symptomatology before and after CO2 inhalation. The plasma concentrations of progesterone, 3α,5α-tetrahydroprogesterone (3α,5α-THPROG=allopregnanolone), 3α,5α-tetrahydrodesoxycorticosterone (3α,5α-THDOC), dehydroepiandrosterone (DHEA), and cortisol were measured 15min and immediately before the onset of CO2 administration as well as immediately, 10, 30, and 50min after the end of CO2 inhalation. Neuroactive steroids were measured in the laboratory of Prof. Biggio in Cagliari, Sardinia, Italy. Neurosteroid levels did not change significantly in both responders and nonresponders before, during, or after CO2 inhalation. These data suggest that neuroactive steroid concentrations before, during, or after CO2 inhalation do not seem to correlate with panic symptomatology during panic-like attacks in subjects not affected by PD, and they therefore do not support the notion that abnormalities in neuroactive steroid secretion are either a cause or an effect of such attacks. Copyright © 2013 Elsevier Ltd. All rights reserved.

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact

PubMed Central

Yang, Tian; Wang, Jinyuan; Pang, Yamei; Dang, Xiaomin; Ren, Hui; Liu, Ya; Chen, Mingwei; Shang, Dong

2016-01-01

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation-induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α-smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor-β1 (TGF-β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme-linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography-mass spectrometry analysis. The deposition of collagen I and α-SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF-β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1-regulated TGF-β1/Smad signaling was involved in silica inhalation-induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling. PMID:27748907

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PubMed

Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Chan, Hak-Kim; Tu, Jiyuan

2017-12-29

Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Nerve growth factor enhances cough via a central mechanism of action.

PubMed

El-Hashim, Ahmed Z; Jaffal, Sahar M; Al-Rashidi, Fatma T; Luqmani, Yunus A; Akhtar, Saghir

2013-08-01

The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5h post-treatment. TrkA mRNA was elevated at 0.5h in the bronchi and at 24h in the brainstem while TRPV1 mRNA was elevated from 0.5h to 24h in brainstem and at 24h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough. Copyright © 2013 Elsevier Ltd. All rights reserved.

Downregulation of the cough reflex by aclidinium and tiotropium in awake and anesthetized rabbits.

PubMed

Mutolo, Donatella; Cinelli, Elenia; Iovino, Ludovica; Pantaleo, Tito; Bongianni, Fulvia

2016-06-01

Long-acting muscarinic receptor antagonists (LAMAs) have been reported to attenuate cough in preclinical and clinical studies. The present study was performed on rabbits to compare aclidinium and tiotropium efficacy in the downregulation of the cough reflex. This reflex was evoked by citric acid inhalation in unanesthetized animals and by both citric acid inhalation and mechanical stimulation of the tracheobronchial tree in anesthetized animals 90 min following the inhalation of each drug (nebulizer output always at 1 mL/min). Aclidinium 4 mg/mL and tiotropium 200 μg/mL inhaled in 1 min proved to have similar protective effect on methacholine-induced bronchoconstriction in anesthetized animals. The total dosage employed for aclidinium and tiotropium was 4 mg and 200 μg, respectively. In awake animals, similar reductions in the cough number were observed following 10-min inhalation of each drug with a slight, not significant tendency to higher antitussive effects for aclidinium. In anesthetized animals, 1-min inhalation of each drug caused similar depressant effects on cough responses induced by both mechanical and chemical stimulation. A complete suppression of cough responses to mechanical stimuli was seen in some preparations. The results strongly suggest that the LAMA-induced downregulation of cough may be mediated not only by transient receptor potential vanilloid type 1 channels, as already reported, but also by acid-sensing ion channels and mechanoreceptors. The route of administration along with the more rapid hydrolysis of aclidinium into inactive metabolites minimize potential systemic side effects and give to this drug a very favorable safety profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice.

PubMed

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

2017-09-01

Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Bronchodilator Effect of Tiotropium via Respimat®Administered with a Spacer in Patients with Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Ogasawara, Takashi; Sakata, Jun; Aoshima, Yoichiro; Tanaka, Kazuki; Yano, Toshiaki; Kasamatsu, Norio

2017-09-15

Objective Among elderly patients with chronic obstructive pulmonary disease (COPD), there are some patients who cannot inhale tiotropium via Respimat ® due to poor hand-lung coordination. This study aimed to examine whether or not tiotropium inhalation therapy using Respimat ® with a spacer increased the forced expiratory volume in 1 s (FEV 1 ) in patients with COPD. Methods A randomized, crossover, single-center study was conducted in 18 patients with stable COPD. Tiotropium (5 μg) via Respimat ® with or without a spacer (AeroChamber ® ) was administered for 2 weeks. Following a 2-week washout period using a transdermal tulobuterol patch (2 mg per day), participants were then crossed over to the other inhalation therapy with respect to spacer use. The trough FEV 1 was measured at every visit using a spirometer. A questionnaire regarding inhalation therapy was administered to patients at the final visit. Results The administration of tiotropium via Respimat ® both with and without a spacer significantly increased the trough FEV 1 from baseline during each treatment period, with mean differences of 115.0±169.6 mL and 92.8±128.1 mL, respectively. There was no significant difference in the change in the trough FEV 1 between the 2 procedures (p=0.66). A total of 86% of patients reported that inhalation using a spacer was not difficult, and more than half also rated both the usage and maintenance of the AeroChamber ® as easy. Conclusion Tiotropium inhalation therapy administered via Respimat ® using a spacer exerted a bronchodilatory effect similar to that observed with tiotropium Respimat ® alone.

Coupled in silico platform: Computational fluid dynamics (CFD) and physiologically-based pharmacokinetic (PBPK) modelling.

PubMed

Vulović, Aleksandra; Šušteršič, Tijana; Cvijić, Sandra; Ibrić, Svetlana; Filipović, Nenad

2018-02-15

One of the critical components of the respiratory drug delivery is the manner in which the inhaled aerosol is deposited in respiratory tract compartments. Depending on formulation properties, device characteristics and breathing pattern, only a certain fraction of the dose will reach the target site in the lungs, while the rest of the drug will deposit in the inhalation device or in the mouth-throat region. The aim of this study was to link the Computational fluid dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in order to predict aerolisolization of different dry powder formulations, and estimate concomitant in vivo deposition and absorption of amiloride hydrochloride. Drug physicochemical properties were experimentally determined and used as inputs for the CFD simulations of particle flow in the generated 3D geometric model of Aerolizer® dry powder inhaler (DPI). CFD simulations were used to simulate air flow through Aerolizer® inhaler and Discrete Phase Method (DPM) was used to simulate aerosol particles deposition within the fluid domain. The simulated values for the percent emitted dose were comparable to the values obtained using Andersen cascade impactor (ACI). However, CFD predictions indicated that aerosolized DPI have smaller particle size and narrower size distribution than assumed based on ACI measurements. Comparison with the literature in vivo data revealed that the constructed drug-specific PBPK model was able to capture amiloride absorption pattern following oral and inhalation administration. The PBPK simulation results, based on the CFD generated particle distribution data as input, illustrated the influence of formulation properties on the expected drug plasma concentration profiles. The model also predicted the influence of potential changes in physiological parameters on the extent of inhaled amiloride absorption. Overall, this study demonstrated the potential of the combined CFD-PBPK approach to model inhaled drug bioperformance, and suggested that CFD generated results might serve as input for the prediction of drug deposition pattern in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology

PubMed Central

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

2016-01-01

Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5–1.0 mg/kg), or MDPV (0.5–1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine. PMID:27277119

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections.

PubMed

Bodier-Montagutelli, Elsa; Morello, Eric; L'Hostis, Guillaume; Guillon, Antoine; Dalloneau, Emilie; Respaud, Renaud; Pallaoro, Nikita; Blois, Hélène; Vecellio, Laurent; Gabard, Jérôme; Heuzé-Vourc'h, Nathalie

2017-08-01

Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation. Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy's clinical positioning in the antimicrobial arsenal against RTIs.

Evaluation of High-Performance Curcumin Nanocrystals for Pulmonary Drug Delivery Both In Vitro and In Vivo

NASA Astrophysics Data System (ADS)

Hu, Liandong; Kong, Dongqian; Hu, Qiaofeng; Gao, Na; Pang, Saixi

2015-10-01

This paper focused on formulating high-performance curcumin spray-dried powders for inhalation (curcumin-DPIs) to achieve a high lung concentration. Curcumin-DPIs were produced using wet milling combined with the spray drying method. The effects of different milling times on particle size and aerodynamic performance were investigated. The curcumin-DPIs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution. Furthermore, the in vivo pharmacokinetic behavior and tissue distribution after pulmonary administration were also evaluated. Results showed that the drug dissolution was significantly enhanced by processing into curcumin-DPIs. The aerodynamic results indicated that the DPIs displayed a good aerosol performance. The plasma curcumin concentration was obviously enhanced by inhalation, and most of the curcumin-DPIs were deposited in the lung. This study demonstrated that inhalation was an effective way to carry drug to the lung, and curcumin-DPIs were hopeful for lung cancer treatment in the future.

Asthma, inhaled corticosteroid treatment, and growth.

PubMed

Ninan, T K; Russell, G

1992-06-01

To evaluate the effects on growth of inhaled corticosteroid treatment (ICT) and of the quality of control of asthma, height velocity was studied in 58 prepubertal children attending a specialist asthma clinic because of chronic asthma that was difficult to control. The height velocity standard deviation (SD) score was maximal when the asthma was well controlled both before (0.01) and after (-0.07) starting ICT. It was least when the asthma was poorly controlled both before (-1.50) and after (-1.55) starting ICT. The effectiveness of control correlated significantly with the height velocity SD score, both before and after ICT was started. No evidence was found that the administration of ICT has an adverse effect on growth.

Challenges of curcumin bioavailability: novel aerosol remedies.

PubMed

Subramani, Parasuraman Aiya; Narala, Venkata R

2013-01-01

Nanoparticles are promising aids for drug delivery for previously challenging diseases, and many incurable ones. Curcumin (diferuloylmethane) is a pleiotropic molecule having various target molecules in the body. Despite its effects, curcumin-based drugs are not readily available in the market because of their low bioavailability. Although dietary intake and knowledge about the potential of curcumin are high in countries like India, studies indicate that the bioavailability problem still persists. However, administration of curcumin through inhalation has received little consideration. In this review we discuss the potential of curcumin, approaches made to overcome the bioavailability challenges, and novel approaches that could be applied in order to deliver curcumin in a pressurized metered dose inhaler (pMDI).

Bench-to-bedside review: Inhaled nitric oxide therapy in adults

PubMed Central

Creagh-Brown, Benedict C; Griffiths, Mark JD; Evans, Timothy W

2009-01-01

Nitric oxide (NO) is an endogenous mediator of vascular tone and host defence. Inhaled nitric oxide (iNO) results in preferential pulmonary vasodilatation and lowers pulmonary vascular resistance. The route of administration delivers NO selectively to ventilated lung units so that its effect augments that of hypoxic pulmonary vasoconstriction and improves oxygenation. This 'Bench-to-bedside' review focuses on the mechanisms of action of iNO and its clinical applications, with emphasis on acute lung injury and the acute respiratory distress syndrome. Developments in our understanding of the cellular and molecular actions of NO may help to explain the hitherto disappointing results of randomised controlled trials of iNO. PMID:19519946

14 CFR 125.207 - Emergency equipment requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Administrator: Contents Quantity Adhesive bandage compressors, 1 in 16 Antiseptic swabs 20 Ammonia inhalants 10 Bandage compressors, 4 in 8 Triangular bandage compressors, 40 in 5 Arm splint, noninflatable 1 Leg splint, noninflatable 1 Roller bandage, 4 in 4 Adhesive tape, 1-in standard roll 2 Bandage scissors 1 Protective latex...

14 CFR 125.207 - Emergency equipment requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Administrator: Contents Quantity Adhesive bandage compressors, 1 in 16 Antiseptic swabs 20 Ammonia inhalants 10 Bandage compressors, 4 in 8 Triangular bandage compressors, 40 in 5 Arm splint, noninflatable 1 Leg splint, noninflatable 1 Roller bandage, 4 in 4 Adhesive tape, 1-in standard roll 2 Bandage scissors 1 Protective latex...

14 CFR 125.207 - Emergency equipment requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Administrator: Contents Quantity Adhesive bandage compressors, 1 in 16 Antiseptic swabs 20 Ammonia inhalants 10 Bandage compressors, 4 in 8 Triangular bandage compressors, 40 in 5 Arm splint, noninflatable 1 Leg splint, noninflatable 1 Roller bandage, 4 in 4 Adhesive tape, 1-in standard roll 2 Bandage scissors 1 Protective latex...

14 CFR 125.207 - Emergency equipment requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Administrator: Contents Quantity Adhesive bandage compressors, 1 in 16 Antiseptic swabs 20 Ammonia inhalants 10 Bandage compressors, 4 in 8 Triangular bandage compressors, 40 in 5 Arm splint, noninflatable 1 Leg splint, noninflatable 1 Roller bandage, 4 in 4 Adhesive tape, 1-in standard roll 2 Bandage scissors 1 Protective latex...

14 CFR 135.177 - Emergency equipment requirements for aircraft having a passenger seating configuration of more...

Code of Federal Regulations, 2010 CFR

2010-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... maintained contents in the specified quantities: Contents Quantity Adhesive bandage compresses, 1-inch 16 Antiseptic swabs 20 Ammonia inhalants 10 Bandage compresses, 4-inch 8 Triangular bandage compresses, 40-inch...

[The importance of endotoxin producing bacterias for practical purposes

PubMed

Schimmel, Dietrich

1994-01-01

Lipopolysaccharides (endotoxin) cause according to resorption out of the intestinal tract or aerogenic inhalation or by a septic infection clinical signs. The clinical reactions are praeshock symptoms, acute forms of shock and death. The experimental intratracheally administration of lipopolysaccharides into calves caused pneumonic lesions without bacterial experimental infection.

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2013 CFR

2013-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2014 CFR

2014-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2012 CFR

2012-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2011 CFR

2011-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

Code of Federal Regulations, 2010 CFR

2010-07-01

... experimental group shall contain at least four animals of each sex. After administration of the test substance... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) PROVISIONAL TEST GUIDELINES Provisional... range should be comparable from group to group. The animals shall be purchased from a reputable dealer...

76 FR 56872 - Information Collection Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

...- controlled quantity of a Class 7 (radioactive) material; (2) more than 25 kg (55 lbs) of a Division 1.1, 1.2... inhalation in hazard zone A; (4) a shipment of hazardous materials in a bulk packaging with a capacity equal... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No...

The Rule of Five for Non-Oral Routes of Drug Delivery: Ophthalmic, Inhalation and Transdermal

PubMed Central

Choy, Young Bin; Prausnitz, Mark R.

2011-01-01

The Rule of Five predicts suitability of drug candidates, but was developed primarily using orally administered drugs. Here, we test whether the Rule of Five predicts drugs for delivery via non-oral routes, specifically ophthalmic, inhalation and transdermal. We assessed 111 drugs approved by FDA for those routes of administration and found that >98% of current non-oral drugs have physicochemical properties within the limits of the Rule of Five. However, given the inherent bias in the dataset, this analysis was not able to assess whether drugs with properties outside those limits are poor candidates. Indeed, further analysis indicates that drugs well outside the Rule of Five limits, including hydrophilic macromolecules, can be delivered by inhalation. In contrast, drugs currently administered across skin fall within more stringent limits than predicted by the Rule of Five, but new transdermal delivery technologies may make these constraints obsolete by dramatically increasing skin permeability. The Rule of Five does appear to apply well to ophthalmic delivery. We conclude that although current non-oral drugs mostly have physicochemical properties within the Rule of Five thresholds, the Rule of Five should not be used to predict non-oral drug candidates, especially for inhalation and transdermal routes. PMID:20967491

Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs.

PubMed

Koch, B L; Edvinsson, A A; Koskinen, L O

1999-01-01

Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.

Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given lipopolysaccharide intratracheally.

PubMed

Hybertson, Brooks M; Chung, Jin H; Fini, Mehdi A; Lee, Young M; Allard, Jenny D; Hansen, Brian N; Cho, Okyong J; Shibao, Gayle N; Repine, John E

2005-04-01

Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a well-characterized lung inflammatory response involving alveolar macrophage activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin E, a lipophilic antioxidant consisting of a family that includes tocopherols and tocotrienols, has previously been shown to have a variety of anti-inflammatory effects, raising interest in its possible uses in disease prevention or therapy. Because aerosol delivery is a specific and rapid way to administer agents to the lungs, the authors undertook to determine whether inhaled vitamin E aerosols would have an anti-inflammatory effect in the lungs. Using a rat model of acute lung inflammation caused by intratracheally administered LPS (10 microg Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol-administered vitamin E, in this case alpha-tocopherol, on several indices of lung inflammation which are increased by LPS treatment. It was found that inhaled alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol, decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1 immunoreactive protein levels in lung lavage, and the number of neutrophils recoverable by lung lavage from rats given LPS intratracheally. These results contribute to the increasing body of work describing immunomodulatory functions of alpha-tocopherol, and support the idea that direct aerosol administration of alpha-tocopherol may play a beneficial role in strategies to control inflammatory lung illnesses.

Searching for the synergistic effect between aclidinium and formoterol: From bench to bedside.

PubMed

Cazzola, Mario; Calzetta, Luigino; Ora, Josuel; Puxeddu, Ermanno; Rogliani, Paola; Matera, Maria Gabriella

2015-10-01

Aim of our study was to understand if the interaction between aclidinium and formoterol administered at therapeutic doses leads to a synergistic rather than additive broncholytic effect. We tested the type of effect ex vivo on isolated human bronchi and then in vivo in COPD patients. The analysis of the interaction between aclidinium and formoterol in vitro was measured by applying the Unified Theory, whereas that in COPD patients was measured by applying the Bliss Independence criterion. Aclidinium and formoterol administered alone completely relaxed human isolated bronchial tissues sub-maximally pre-contracted with ACh in a concentration-dependent manner with similar potency (EC50: aclidinium 4.64 ± 0.78 nM, formoterol 2.71 ± 0.21), whereas the interaction of aclidinium plus formoterol produced moderate to strong synergism. Changes in FEV1 values showed that inhaled aclidinium and formoterol induced a significant and time-dependent bronchodilatory effect during the study time. The inhalation of aclidinium and formoterol in combination significantly anticipated at 5 min post-administration the bronchodilatory effect of FEV1, compared with the effect of drugs administered alone. There was a synergistic interaction for FEV1 at 5 min and from 120 min to 240 min post-inhalation, whereas from 30 min to 60 min post-administration the drug interaction was additive. This study shows that aclidinium and formoterol can produce a significant synergistic interaction that may have a role also in the clinic setting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long-term effect of budesonide on hypothalamic-pituitary-adrenal axis function in children with mild to moderate asthma.

PubMed

Bacharier, Leonard B; Raissy, Hengameh H; Wilson, Laura; McWilliams, Bennie; Strunk, Robert C; Kelly, H William

2004-06-01

To determine the safety of long-term (36 months) administration of an inhaled corticosteroid (budesonide) on hypothalamic-pituitary-adrenal (HPA) axis function in children with mild to moderate asthma. This was an ancillary study of the Childhood Asthma Management Program (CAMP). Sixty-three children who had mild to moderate asthma and were enrolled in CAMP underwent evaluation of HPA axis function before and 12 and 36 months after receiving continuous therapy with either an inhaled anti-inflammatory agent (budesonide 400 microg/day or nedocromil 16 mg/day) or placebo. HPA axis function was assessed by serum cortisol levels 30 and 60 minutes after 0.25 mg of adrenocorticotrophic hormone (ACTH) and 24-hour urinary free cortisol excretion. There were no differences in serum cortisol levels after ACTH stimulation between treatment groups, regardless of time after ACTH administration or months of follow-up. Urinary cortisol excretion per body surface area was similar in both treatment groups at 36 months, after adjusting for age at randomization, race, gender, and clinic. Cumulative inhaled corticosteroid exposure did not influence serum cortisol response to ACTH or urinary free cortisol excretion at 36 months. We found no effects of chronic budesonide treatment at a dose of 400 micro g/day on HPA axis function in children with mild to moderate asthma and demonstrated the absence of a cumulative effect on HPA axis function over a 3-year period.

The preventive effect of nedocromil or furosemide alone or in combination on exercise-induced asthma in children.

PubMed

Novembre, E; Frongia, G; Lombardi, E; Veneruso, G; Vierucci, A

1994-08-01

Recent evidence suggests that inhaled nedocromil and furosemide are effective in preventing asthma by ultrasonically nebulized distilled water, allergen, and exercise. There are, however, no studies that compare the effects of these two drugs. The aim of this study was to investigate the effect of inhaled furosemide (30 mg), nedocromil (4 mg), the combination of these two drugs, and placebo aerosol in preventing exercise-induced asthma. Twenty-four children with exercise-induced asthma, aged 6 to 16 years, performed a treadmill test before and 20 minutes after a single dose of drug(s) in a double-blind trial. Lung function measurements were taken before drug administration, before the exercise test (20 minutes after drug administration), and then 2, 4, 6, 8, 10, 15, 20, and 30 minutes after the exercise test. Both active drugs performed significantly better than placebo. In fact, the exercise challenge resulted in a mean maximum fall in forced expiratory volume in 1 second of 28.46% +/- 13.84% after administration of placebo, but of only 15.42% +/- 8.35% after administration of nedocromil (p < 0.001) and of 11.37% +/- 9.14% after administration of furosemide (p < 0.001). When the two drugs were given together, there was a statistically significant additive effect because the mean maximum fall in forced expiratory volume in 1 second was 5.75% +/- 3.57% (nedocromil vs nedocromil + fluorsemide: p < 0.001; furosemide vs nedocromil + furosemide: p < 0.01). This study suggests that nedocromil and furosemide provide a comparable effect in preventing exercise-induced asthma in children. The combined administration of the two drugs significantly increases the protective effects, suggesting a potential therapeutic use.

A Comparison of the Pharmacokinetics and Pulmonary Lymphatic Exposure of a Generation 4 PEGylated Dendrimer Following Intravenous and Aerosol Administration to Rats and Sheep.

PubMed

Ryan, Gemma M; Bischof, Robert J; Enkhbaatar, Perenlei; McLeod, Victoria M; Chan, Linda J; Jones, Seth A; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

2016-02-01

Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep. Lung-derived lymph could not be sampled in rats and so lymphatic transport of the dendrimer from the lung was assessed in sheep. Higher plasma concentrations were achieved when dendrimer was administered to the lungs of rats as a liquid instillation when compared to an aerosol. Plasma pharmacokinetics were similar between sheep and rats, although some differences in disposition patterns were evident. Unexpectedly, less than 0.5% of the aerosol dose was recovered in pulmonary lymph. The data suggest that rats provide a relevant model for assessing the pharmacokinetics of inhaled macromolecules prior to evaluation in larger animals, but that the pulmonary lymphatics are unlikely to play a major role in the absorption of nanocarriers from the lungs.

A review of pitfalls and progress in chelation treatment of metal poisonings.

PubMed

Andersen, Ole; Aaseth, Jan

2016-12-01

Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals. Also, diethyl dithiocarbamate (DDC) has been used as antidote in acute experimental animal parenteral Cd poisoning, and both DDC and tetraethylthiuram disulfide (TTD, disulfiram, Antabuse) have been used in nickel allergic patients. However, even one dose of DDC given immediately after oral Cd or Ni increased their brain uptake considerably. The calcium salt of ethylenediamminetetraacetic acid (CaEDTA) but not dimercaptosuccinic acid (DMSA) increased the brain uptake of Pb. In oral Cd or Hg poisoning, early oral administration of DMSA or dimercaptopropane sulfonate (DMPS) increased survival and reduced intestinal metal uptake. Oral administration of Prussian Blue or resins with fixed chelating groups that are not absorbed offer chelation approaches for decorporation after oral exposure to various metals. Diethylenetriaminepentaacetic acid (DTPA) nebulizers for pulmonary chelation after inhalation exposure need further development. Also, combined chelation with more than one compound may offer extensive advances. Solid knowledge on the chemistry of metal chelates together with relevant animal experiments should guide development of chelation procedures to alleviate and not aggravate the clinical status of poisoned patients. Copyright © 2016 Elsevier GmbH. All rights reserved.

Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

PubMed

Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; Flegel, Ron; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

2014-10-01

Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A specific and sensitive HPLC-MS/MS micromethod for milrinone plasma levels determination after inhalation in cardiac patients.

PubMed

Gavra, Paul; Nguyen, Anne Q-N; Theoret, Yves; Litalien, Catherine; Denault, André Y; Varin, France

2014-10-01

Milrinone administered through inhalation is an emerging method aimed at specifically reducing pulmonary hypertension without affecting systemic pressures. Its administration has been shown to be useful both in patients undergoing cardiac surgery and for persistent pulmonary hypertension of the newborn. These populations are prone to receive many concomitant medications and/or blood sampling may require a low volume quantification method. To address these issues in view of pharmacokinetic studies, this article aims to develop and validate a specific and sensitive analytical assay using high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the quantification of milrinone plasma concentrations after inhalation in patients undergoing cardiac surgery. Plasma samples (50 μL) were extracted using ethyl acetate. Milrinone was separated on a C18 analytical column at 50°C. The mobile phase consisted of methanol and 10 mM ammonium acetate (45:55 vol/vol). The electrospray was operated in the negative ionization mode and monitored the following mass transitions: m/z 212.1 → 140.0 at 36 eV for milrinone and m/z 252.1 → 156.1 at 32 eV for olprinone. Calibration curves followed a quadratic regression in the concentration range of 0.3125-640 ng/mL. The lower limit of quantification is 0.3125 ng/mL and is based on a low plasma volume of 50 μL. Mean drug recovery and accuracy were ≥72.3% and 96.0%, respectively. Intraday and interday precision coefficient of variation (%) was ≤7.4% and ≤11.5%, respectively. The specificity allowed milrinone quantification in the multidrug administration conditions of cardiopulmonary bypass. This validated micromethod proved to be highly sensitive and specific while using a low volume of plasma. Its low volume and its lower limit of quantification indicate that this approach is suitable for further characterization of milrinone pharmacokinetics in both adults (inhalation) and neonates.

The Combination of Cobinamide and Sulfanegen Is Highly Effective in Mouse Models of Cyanide Poisoning

PubMed Central

Chan, Adriano; Crankshaw, Daune L.; Monteil, Alexandre; Patterson, Steven E.; Nagasawa, Herbert T.; Briggs, Jackie E.; Kozocas, Joseph A.; Mahon, Sari B.; Brenner, Matthew; Pilz, Renate B.; Bigby, Timothy D.; Boss, Gerry R.

2013-01-01

SUMMARY Context Cyanide poisoning is a major contributor to death in smoke inhalation victims and accidental exposure to cyanide occurs in a variety of industries. Moreover, cyanide has the potential to be used by terrorists, particularly in a closed space such as an airport or train station. Current therapies for cyanide poisoning must be given by intravenous administration, limiting their use in treating mass casualties. Objective We are developing two new cyanide antidotes—cobinamide, a vitamin B12 analog, and sulfanegen, a 3-mercaptopyruvate prodrug. Both drugs can be given by intramuscular administration, and therefore could be used to treat a large number of people quickly. We now asked if the two drugs would have an augmented effect when combined. Materials and Methods We used a non-lethal and two different lethal models of cyanide poisoning in mice. The non-lethal model assesses neurologic recovery by quantitatively evaluating the innate righting reflex time of a mouse. The two lethal models are a cyanide injection and a cyanide inhalation model. Results We found that the two drugs are at least additive when used together in both the non-lethal and lethal models: at doses where all animals died with either drug alone, the combination yielded 80 and 40% survival in the injection and inhalation models, respectively. Similarly, drug doses that yielded 40% survival with either drug alone yielded 80 and 100% survival in the injection and inhalatiion models, respectively. As part of the inhalation model, we developed a new paradigm in which animals are exposed to cyanide gas, injected intramuscularly with antidote, and then re-exposed to cyanide gas. This simulates cyanide exposure of a large number of people in a closed space, because people would remain exposed to cyanide, even after receiving an antidote. Conclusion The combination of cobinamide and sulfanegen shows great promise as a new approach to treating cyanide poisoning. PMID:21740135

Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rancourt, Raymond C., E-mail: raymond.rancourt@ucdenver.edu; Veress, Livia A., E-mail: livia.veress@ucdenver.edu; Ahmad, Aftab, E-mail: aftab.ahmad@ucdenver.edu

Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5 mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O{sub 2} saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin–antithrombin complex (TAT), active plasminogen activatormore » inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury. - Highlights: • TFPI administration to rats after mustard inhalation reduces airway cast formation. • Inhibition of thrombin activation is the likely mechanism for limiting casts. • Rats given TFPI had improved tissue oxygenation, and mortality was prevented.« less

Potential for enhancing external beam radiotherapy for lung cancer using high-Z nanoparticles administered via inhalation

NASA Astrophysics Data System (ADS)

Hao, Yao; Altundal, Yucel; Moreau, Michele; Sajo, Erno; Kumar, Rajiv; Ngwa, Wilfred

2015-09-01

Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo-generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5-14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.

Cardiotoxic (Arrhythmogenic) Effects of 1,1-Difluoroethane Due to Electrolyte Imbalance and Cardiomyocyte Damage.

PubMed

Joshi, Kaushal; Barletta, Michael; Wurpel, John

2017-06-01

Inhalant abuse is the intentional inhalation of chemical vapors to attain euphoric effects. Many common household products are abused by inhalation and one is 1,1-difluoroethane (DFE), which is a halogenated hydrocarbon used in refrigeration, dust-off spray, and airbrush painting. Although many human DFE abuse cases have been studied, the etiology and mechanism of sudden death is still unknown. In this study, an animal model was used to simulate the human conditions of DFE inhalation abuse that results in sudden death.Current research targets mechanistic studies involving electrolyte changes and cardiomyocyte damage after DFE administration in vivo. To investigate these changes, Sprague Dawley rats (N = 6) were exposed to 30 seconds of 20 L/min of DFE in multiple doses. Isoflurane acted as a control. Two additional groups, epinephrine and epinephrine + DFE, were included to simulate the clinical condition of DFE abuse. Plasma sodium, potassium, calcium, and magnesium levels were measured, followed by lactate dehydrogenase, creatine kinase, and cardiac troponin I levels. In addition, oxidative stress markers were also evaluated in all animal groups. Electrolyte levels showed a significant rise in plasma potassium and magnesium levels for the treated groups. In addition, lactate dehydrogenase, creatine kinase, and cardiac troponin I levels in DFE and epinephrine + DFE administered rats were significantly elevated as compared with control. Some oxidative stress makers were also elevated significantly in treatment groups. Furthermore, histopathological analysis showed hyperemia/congestion in treated rats.These results support cardiotoxic effects indicating that DFE results in fatal arrhythmias, and the study can be important during clinical cases involving inhalant abuse.

A novel continuous powder aerosolizer (CPA) for inhalative administration of highly concentrated recombinant surfactant protein-C (rSP-C) surfactant to preterm neonates.

PubMed

Pohlmann, G; Iwatschenko, P; Koch, W; Windt, H; Rast, M; de Abreu, M Gama; Taut, F J H; De Muynck, C

2013-12-01

In pulmonary medicine, aerosolization of substances for continuous inhalation is confined to different classes of nebulizers with their inherent limitations. Among the unmet medical needs is the lack of an aerosolized surfactant preparation for inhalation by preterm neonates, to avoid the risks associated with endotracheal intubation and surfactant bolus instillation. In the present report, we describe a high-concentration continuous powder aerosolization system developed for delivery of inhalable surfactant to preterm neonates. The developed device uses a technique that allows efficient aerosolization of dry surfactant powder, generating a surfactant aerosol of high concentration. In a subsequent humidification step, the heated aerosol particles are covered with a surface layer of water. The wet surfactant aerosol is then delivered to the patient interface (e.g., nasal prongs) through a tube. The performance characteristics of the system are given as mass concentration, dose rate, and size distribution of the generated aerosol. Continuous aerosol flows of about 0.84 L/min can be generated from dry recombinant surfactant protein-C surfactant, with concentrations of up to 12 g/m(3) and median particle sizes of the humidified particles in the range of 3 to 3.5 μm at the patient interface. The system has been successfully used in preclinical studies. The device with its continuous high-concentration delivery is promising for noninvasive delivery of surfactant aerosol to neonates and has the potential for becoming a versatile disperser platform closing the gap between continuously operating nebulizers and discontinuously operating dry powder inhaler devices.

77 FR 55845 - Anti-Infective Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... and Drug Administration (FDA). The meeting will be open to the public. Name of Committee: Anti... indication of treatment of inhalational anthrax. FDA intends to make background material available to the... of the general nature of the evidence or arguments they wish to present, the names and addresses of...

Toxicologic and Analytical Studies with T-2 and Related Trichothecene Mycotoxins

DTIC Science & Technology

1983-03-01

study is to assess the nature of T-2 induced shock using intravascular and inhalation routes of administration. To accomplish this goal, we investi...this data. In addition, a bone marrow response is absent as evidenced by the lack of significant increase in irm- nature neutrophils (band cells). The

30 CFR 71.700 - Inhalation hazards; threshold limit values for gases, dust, fumes, mists, and vapors.

Code of Federal Regulations, 2014 CFR

2014-07-01

... gases, dust, fumes, mists, and vapors. 71.700 Section 71.700 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY HEALTH STANDARDS-SURFACE COAL MINES AND... limit values adopted by the American Conference of Governmental Industrial Hygienists in “Threshold...

Methods of inducing conditioned food aversion to Baccharis coridifolia (mio-mio) in cattle

USDA-ARS?s Scientific Manuscript database

Three experiments were performed to determine the efficacy of various methods of averting naïve cattle to prevent Baccharis coridifolia poisoning: forced oral administration of 0.5 g kg-1 body weight of fresh B. coridifolia; forced inhalation of the smoke from burning B. coridifolia and rubbing the ...

Feasibility of nitric oxide administration by neonatal helmet-CPAP: a bench study.

PubMed

Trevisanuto, Daniele; Doglioni, Nicoletta; Micaglio, Massimo; Zanardo, Vincenzo

2007-09-01

Inhaled nitric oxide (NO) may have a role in the treatment of preterm infants with respiratory failure. We evaluated the feasibility of administering NO therapy by a new continuous positive airway pressure (CPAP) system (neonatal helmet-CPAP). While maintaining a constant total flow of 8, 10, and 12 l.min(-1), NO concentrations were progressively increased to 5, 10, 20, and 40 p.p.m. in the neonatal helmet-CPAP pressure chamber (5 cmH2O). NO, NO2, and O2 concentrations were measured in the pressure chamber and the immediate external environment. In the chamber, NO2 levels remained low (

'Flooding' of the lungs and severe dyspnea in a patient with bronchoalveolar carcinoma.

PubMed

Keizer, Ron J; Beijnen, Jos H; Baas, Paul

2011-09-01

In this case report, we describe a patient with bronchoalveolar carcinoma that experienced severe bronchorrhea and dyspnea after inhalation of N-acetylcysteine. The adverse reactions occurred both after oral and nebulized administration of N-acetylcysteine, resulting in severe dyspnea and the feeling of 'drowning'. Bronchorrhea has previously been reported as an uncommon but serious complication of bronchoalveolar carcinoma. We strongly suspect the administration of N-acetylcysteine to be implicated, as the complications occurred immediately after administration of this drug. As the patient suffered from hyperhomocysteinemia, we speculate that an additive or synergistic interaction with homocysteine may have been involved as well.

A review on recent technologies for the manufacture of pulmonary drugs.

PubMed

Hadiwinoto, Gabriela Daisy; Lip Kwok, Philip Chi; Lakerveld, Richard

2018-01-01

This review discusses recent developments in the manufacture of inhalable dry powder formulations. Pulmonary drugs have distinct advantages compared with other drug administration routes. However, requirements of drugs properties complicate the manufacture. Control over crystallization to make particles with the desired properties in a single step is often infeasible, which calls for micronization techniques. Although spray drying produces particles in the desired size range, a stable solid state may not be attainable. Supercritical fluids may be used as a solvent or antisolvent, which significantly reduces solvent waste. Future directions include application areas such as biopharmaceuticals for dry powder inhalers and new processing strategies to improve the control over particle formation such as continuous manufacturing with in-line process analytical technologies.

Generally Recognized as Safe: Uncertainty Surrounding E-Cigarette Flavoring Safety.

PubMed

Sears, Clara G; Hart, Joy L; Walker, Kandi L; Robertson, Rose Marie

2017-10-23

Despite scientific uncertainty regarding the relative safety of inhaling e-cigarette aerosol and flavorings, some consumers regard the U.S. Food and Drug Administration's "generally recognized as safe" (GRAS) designation as evidence of flavoring safety. In this study, we assessed how college students' perceptions of e-cigarette flavoring safety are related to understanding of the GRAS designation. During spring 2017, an online questionnaire was administered to college students. Chi-square p -values and multivariable logistic regression were employed to compare perceptions among participants considering e-cigarette flavorings as safe and those considering e-cigarette flavorings to be unsafe. The total sample size was 567 participants. Only 22% knew that GRAS designation meant that a product is safe to ingest, not inhale, inject, or use topically. Of participants who considered flavorings to be GRAS, the majority recognized that the designation meant a product is safe to ingest but also considered it safe to inhale. Although scientific uncertainty on the overall safety of flavorings in e-cigarettes remains, health messaging can educate the public about the GRAS designation and its irrelevance to e-cigarette safety.

Nanotechnology and pharmaceutical inhalation aerosols.

PubMed

Patel, A R; Vavia, P R

2007-02-01

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

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin.

PubMed

Andrade, Fernanda; das Neves, José; Gener, Petra; Schwartz, Simó; Ferreira, Domingos; Oliva, Mireia; Sarmento, Bruno

2015-10-01

Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 μm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

An injection and mixing element for delivery and monitoring of inhaled nitric oxide.

PubMed

Martin, Andrew R; Jackson, Chris; Fromont, Samuel; Pont, Chloe; Katz, Ira M; Caillobotte, Georges

2016-08-30

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator used primarily in the critical care setting for patients concurrently supported by invasive or noninvasive positive pressure ventilation. NO delivery devices interface with ventilator breathing circuits to inject NO in proportion with the flow of air/oxygen through the circuit, in order to maintain a constant, target concentration of inhaled NO. In the present article, a NO injection and mixing element is presented. The device borrows from the design of static elements to promote rapid mixing of injected NO-containing gas with breathing circuit gases. Bench experiments are reported to demonstrate the improved mixing afforded by the injection and mixing element, as compared with conventional breathing circuit adapters, for NO injection into breathing circuits. Computational fluid dynamics simulations are also presented to illustrate mixing patterns and nitrogen dioxide production within the element. Over the range of air flow rates and target NO concentrations investigated, mixing length, defined as the downstream distance required for NO concentration to reach within ±5 % of the target concentration, was as high as 47 cm for the conventional breathing circuit adapters, but did not exceed 7.8 cm for the injection and mixing element. The injection and mixing element has potential to improve ease of use, compatibility and safety of inhaled NO administration with mechanical ventilators and gas delivery devices.

Localized demodicosis due to Demodex cati on the muzzle of two cats treated with inhalant glucocorticoids.

PubMed

Bizikova, Petra

2014-06-01

Feline demodicosis due to Demodex cati is a rare skin disease often associated with concurrent disease and generalized immunosuppression. Local immunosuppression due to the application of topical immunomodulatory drugs, such as glucocorticoids and tacrolimus, or by tumour cells has been suggested as a potential trigger for development of localized demodicosis in humans and animals. The goal was to describe two cats with asthma that developed localized demodicosis on the muzzle as a result of chronic therapy with a glucocorticoid administered via dispensing inhaler mask. In both cats, the muzzle area exposed to the fluticasone-dispensing chamber exhibited patchy alopecia, mild erythema, crusting and scaling. Deep skin scraping revealed D. cati. Discontinuation or reduction of fluticasone and administration of milbemycin resulted in resolution of clinical signs within 2 months in both cats. A negative skin scrape was obtained after 7 months of milbemycin in one of the cats. Demodicosis should be considered as a possible differential diagnosis in cats with primary alopecia or other skin lesions on the face exposed to inhalant glucocorticoids. Minimization of contact between the inhalant glucocorticoid and the skin can be achieved by wiping residual powder from the face and by keeping the mask tightly pressed to the skin to avoid contact with the surrounding area. © 2014 ESVD and ACVD.

Voluntary inhalation of methamphetamine: a novel strategy for studying intake non-invasively.

PubMed

Juarez-Portilla, C; Kim, R D; Robotham, M; Tariq, M; Pitter, M; LeSauter, J; Silver, R

2017-03-01

The abuse of the psychostimulant methamphetamine (MA) is associated with substantial costs and limited treatment options. To understand the mechanisms that lead to abuse, animal models of voluntary drug intake are crucial. We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice. Mice were maintained in their home cages and allowed daily 1 h access to an attached tunnel leading to a test chamber in which nebulized MA was available. Restated, if they went to the nebulizing chamber, they self-administered MA by inhalation. This protocol was compared to injected and to imposed exposure to nebulized MA, in a series of seven experiments. We established a concentration of nebulized MA at which motor activity increases following voluntary intake resembled that following MA injection and imposed inhalation. We found that mice regulated their exposure to MA, self-administering for shorter durations when concentrations of nebulized MA were increased. Mice acquire the available MA by repeatedly running in and out of the nebulizing chamber for brief bouts of intake. Such exposure to nebulized MA elevated plasma MA levels. There was limited evidence of sensitization of locomotor activity. Finally, blocking access to the wheel did not affect time spent in the nebulizing chamber. We conclude that administration of MA by nebulization is an effective route of self-administration, and our new protocol represents a promising tool for examining the transitions from first intake to long-term use and its behavioral and neural consequences in a non-invasive protocol.

Diethylene-triamine-penta-acetate administration protocol for radiological emergency medicine in nuclear fuel reprocessing plants.

PubMed

Jin, Yutaka

2008-01-01

Inhalation therapy of diethylene-triamine-penta-acetate (DTPA) should be initiated immediately to workers who have significant incorporation of plutonium, americium or curium in the nuclear fuel reprocessing plant. A newly designed electric mesh nebulizer is a small battery-operated passive vibrating mesh device, in which vibrations in an ultrasonic horn are used to force drug solution through a mesh of micron-sized holes. This nebulizer enables DTPA administration at an early stage in the event of a radiation emergency from contamination from the above radioactive metals.

Iatrogenic Cushing's syndrome caused by intranasal steroid use.

PubMed

Dursun, Fatma; Kirmizibekmez, Heves

2017-01-01

Cushing's syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. This is the case of a 6-year-old child who developed Cushing's syndrome after intranasal application of dexamethasone sodium phosphate for a period of 6 months. Pediatricians and other clinical practitioners should be aware that high-dose and long-term nasal steroid administration may cause iatrogenic Cushing's syndrome characterized by complications of glucocorticoid excess as well as serious and even life-threatening complications of adrenal insufficiency.

The expanding role of aerosols in systemic drug delivery, gene therapy, and vaccination.

PubMed

Laube, Beth L

2005-09-01

Aerosolized medications have been used for centuries to treat respiratory diseases. Until recently, inhalation therapy focused primarily on the treatment of asthma and chronic obstructive pulmonary disease, and the pressurized metered-dose inhaler was the delivery device of choice. However, the role of aerosol therapy is clearly expanding beyond that initial focus. This expansion has been driven by the Montreal protocol and the need to eliminate chlorofluorocarbons (CFCs) from traditional metered-dose inhalers, by the need for delivery devices and formulations that can efficiently and reproducibly target the systemic circulation for the delivery of proteins and peptides, and by developments in medicine that have made it possible to consider curing lung diseases with aerosolized gene therapy and preventing epidemics of influenza and measles with aerosolized vaccines. Each of these drivers has contributed to a decade or more of unprecedented research and innovation that has altered how we think about aerosol delivery and has expanded the role of aerosol therapy into the fields of systemic drug delivery, gene therapy, and vaccination. During this decade of innovation, we have witnessed the coming of age of dry powder inhalers, the development of new soft mist inhalers, and improved pressurized metered-dose inhaler delivery as a result of the replacement of CFC propellants with hydrofluoroalkane. The continued expansion of the role of aerosol therapy will probably depend on demonstration of the safety of this route of administration for drugs that have their targets outside the lung and are administered long term (eg, insulin aerosol), on the development of new drugs and drug carriers that can efficiently target hard-to-reach cell populations within the lungs of patients with disease (eg, patients with cystic fibrosis or lung cancer), and on the development of devices that improve aerosol delivery to infants, so that early intervention in disease processes with aerosol therapy has a high probability of success.

Drug-induced regulatory overcompensation has motivational consequences: Implications for homeostatic and allostatic models of drug addiction

PubMed Central

Ramsay, Douglas S; Woods, Stephen C; Kaiyala, Karl J

2014-01-01

Initial administration of 60% nitrous oxide (N2O) at 21°C ambient temperature reduces core temperature (Tc) in rats, but tolerance develops to this hypothermic effect over several administrations. After additional N2O administrations, a hyperthermic overcompensation (sign-reversal) develops such that Tc exceeds control levels during N2O inhalation. This study investigated whether rats would employ behavioral thermoregulation to facilitate, or oppose, a previously acquired hyperthermic overcompensation during N2O administration. To establish a hyperthermic sign-reversal, male Long-Evans rats (N = 12) received 10 3-h administrations of 60% N2O while housed in a gas-tight, live-in, “inactive” thermal gradient (∼21°C). Following the tenth N2O exposure, the thermal gradient was activated (range of 10–37°C), and rats received both a control gas session and a 60% N2O test session in counterbalanced order. Mean Tc during N2O inhalation in the inactive gradient was reliably hypothermic during the first exposure but was reliably hyperthermic by the tenth exposure. When subsequently exposed to 60% N2O in the active gradient, rats selected a cooler Ta, which blunted the hyperthermic sign-reversal and lowered Tc throughout the remainder of the N2O exposure. Thus, autonomic heat production effectors mediating the hyperthermia were opposed by a behavioral effector that promoted increased heat loss via selection of a cooler ambient temperature. These data are compatible with an allostatic model of drug addiction that suggests that dysregulatory overcompensation in the drugged-state may motivate behaviors (e.g., drug taking) that oppose the overcompensation, thereby creating a vicious cycle of escalating drug consumption and recurring dysregulation. PMID:25938126

Asbestos in Our Schools. Taming the Silent Killer. A Handbook for Association Leaders Produced by NEA.

ERIC Educational Resources Information Center

National Education Association, Washington, DC.

In 1984, the U. S. Environmental Protection Agency (EPA) estimated that friable asbestos-containing materials were present in 31,000 school buildings throughout the country. Once inhaled, asbestos fibers may remain in the lungs indefinitely and can lead to various diseases. This handbook is intended to provide administrators--in nontechnical…

New H1/H3 antagonists for treating allergic rhinitis: WO2010094643.

PubMed

Norman, Peter

2011-03-01

This application claims dual receptor specificity antihistamines, active as H(1) and H(3) antagonists, which additionally have a long duration of action that renders them suitable for once daily administration via inhalation for the treatment of allergic rhinitis. The compounds lack CNS penetration and have a high affinity for both histamine receptors.

Reduction of carboxyhaemoglobin levels in the venous blood of cigarette smokers following the administration of carbogen.

PubMed

Macdonald, Graham; Kondor, Natalie; Yousefi, Vandad; Green, Alex; Wong, Frances; Aquino-Parsons, Christina

2004-12-01

Cigarette smokers have high carboxyhaemoglobin levels which can promote tumour radioresistance. Inhalation of carbogen gas shortens the half-life of carboxyhaemoglobin, increasing tumour radiosensitivity in animal models. Breathing 2.5% carbogen for 30 min results in a greater reduction in venous blood COHb levels than breathing 5% carbogen for 7 min.

Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates.

PubMed

Shah, Vibhuti S; Ohlsson, Arne; Halliday, Henry L; Dunn, Michael

2017-01-04

Chronic lung disease (CLD) remains a common complication among preterm infants. There is increasing evidence that inflammation plays an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties, corticosteroids are an attractive intervention strategy. However, there are growing concerns regarding short- and long-term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects. To determine the impact of inhaled corticosteroids administered to preterm infants with birth weight up to 1500 grams (VLBW) beginning in the first two weeks after birth for the prevention of CLD as reflected by the requirement for supplemental oxygen at 36 weeks' postmenstrual age (PMA). Randomised and quasi-randomised trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12) in the Cochrane Library (searched 5 January 2016), MEDLINE (1966 to 5 January 2016), Embase (1980 to 5 January 2016), CINAHL (1982 to 5 January 2016), reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web-site (1990 to May 2016). We included in this review randomised controlled trials of inhaled corticosteroid therapy initiated within the first two weeks of life in VLBW preterm infants. We evaluated data regarding clinical outcomes, including: CLD at 28 days or 36 weeks' PMA; mortality; combined outcome of death or CLD at 28 days of age and at 36 weeks' PMA; the need for systemic corticosteroids; failure to extubate within 14 days; and adverse effects of corticosteroids. All data were analysed using Review Manager (RevMan) 5. Meta-analyses were performed using relative risk (RR) and risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, the number needed to treat for an additional beneficial outcome (NNTB) was calculated. We used the GRADE approach to assess the quality of evidence. According to GRADE the quality of the studies was moderate. Three additional trials are included in this update. The present review includes data analyses based on 10 qualifying trials that enrolled 1644 neonates. There was no significant difference in the incidence of CLD at 36 weeks' PMA in the inhaled steroid versus the placebo group (5 trials, 429 neonates) among all randomised (typical RR 0.97, 95% CI 0.62 to 1.52; typical RD -0.00, 95% CI -0.07 to 0.06). There was no heterogeneity for this outcome (typical RR I² = 11%; typical RD I² = 0%). There was a significant reduction in the incidence of CLD at 36 weeks' PMA among survivors (6 trials, 1088 neonates) (typical RR 0.76, 95% CI 0.63 to 0.93; typical RD -0.07, 95% CI -0.13 to -0.02; NNTB 14, 95% CI 8 to 50). There was a significant reduction in the combined outcome of death or CLD at 36 weeks' PMA among all randomised neonates (6 trials, 1285 neonates) (typical RR 0.86, 95% CI 0.75 to 0.99; typical RD -0.06, 95% CI -0.11 to -0.00) (P = 0.04); NNTB 17, 95% CI 9 to infinity). There was no significant heterogeneity for any of these analyses (I² = 0%). A lower rate of reintubation was noted in the inhaled steroid group compared with the control group in one study. There were no statistically significant differences in short-term complications between groups and no differences in adverse events at long-term follow-up reported. Long-term follow-up of infants enrolled in the study by Bassler 2015 is ongoing. Based on this updated review, there is increasing evidence from the trials reviewed that early administration of inhaled steroids to VLBW neonates is effective in reducing the incidence of death or CLD at 36 weeks' PMA among either all randomised infants or among survivors. Even though there is statistical significance, the clinical relevance is of question as the upper CI limit for the outcome of death or CLD at 36 weeks' PMA is infinity. The long-term follow-up results of the Bassler 2015 study may affect the conclusions of this review. Further studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short- and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.

Pulmonary delivery of a GLP-1 receptor agonist, BMS-686117.

PubMed

Qian, Feng; Mathias, Neil; Moench, Paul; Chi, Cecilia; Desikan, Sridhar; Hussain, Munir; Smith, Ronald L

2009-01-21

Alternate delivery route of therapeutic peptides is an attractive non-invasive option to patients who must chronically self-administer their medication through injections. In recent years, much attention has centered on pulmonary peptide delivery of peptide drugs such as insulin and GLP-1 mimetic peptides in the treatment of type II diabetes. In this study, we assessed the feasibility of delivering BMS-686117, an 11-mer GLP-1 receptor peptide agonist, to the lung in rats via intratracheal administration. The pharmacokinetic profiles of three spray-dried, prototype inhaled powder formulations, 80/20 BMS-686117/trehalose (I), 100% BMS-686117 (II), and 20/80 BMS-686117/mannitol (III), as well as a lyophilized BMS-686117 powder, were compared with intravenously and subcutaneously administered peptide. The spray-dried formulations were mostly spherical particles with narrow particle size distribution between 2 to 10 microm, which are better suited for inhalation delivery than the lyophilized, irregular shape powder with a wide particle size distribution between 2 to 100 microm. Prototype III exhibited the best physical characteristics and in vivo performance, with bioavailability of 45% relative to subcutaneous administration. The T(max) for lung delivered peptide formulations were almost twice as fast as subcutaneous injection, suggesting potential for rapid absorption and onset of action. This study demonstrated that pulmonary delivery is a promising, non-invasive route for the administration of BMS-686117.

Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.

PubMed

Ohta, K; Yamashita, N; Tajima, M; Miyasaka, T; Nakano, J; Nakajima, M; Ishii, A; Horiuchi, T; Mano, K; Miyamoto, T

1999-11-01

Inhaled pollutants were recently shown to be responsible for an increased incidence of airway allergic diseases, including asthma. A common feature of all forms of asthma is airway hyperresponsiveness. Our purpose was to elucidate the effects of diesel exhaust particulate (DEP), one of the most prevalent inhaled pollutants, on airway responsiveness. A/J and C57Bl/6 mice were used; the former are genetically predisposed to be hyperresponsive to acetylcholine, whereas the latter are not. DEP was administered intranasally for 2 weeks, after which pulmonary function was analyzed by whole-body plethysmography. Intranasal administration of DEP increased airway responsiveness to acetylcholine in both A/J and C57Bl/6 mice and induced displacement of ciliated epithelial cells by mucus-secreting Clara cells. The effect was mediated by M(3) muscarinic receptors. Acetylcholine-evoked bronchial constriction was reversed by administration of terbutaline, a beta(2)-adrenergic antagonist, which is also characteristic of human asthma. Intranasal administration of antibody raised against GM-CSF abolished DEP-evoked increases in airway responsiveness and Clara cell hyperplasia. The antibody raised against IL-4 also inhibited DEP-evoked increases in airway responsiveness. However, it was to a lesser extent compared with antibody against GM-CSF. In addition, DEP stimulated GM-CSF messenger RNA expression in the lung. DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.

Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.

PubMed

Che, Magnus M; Chanda, Soma; Song, Jian; Doctor, Bhupendra P; Rezk, Peter E; Sabnekar, Praveena; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

2011-07-01

Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.

Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.

PubMed

Blondin, Marie-Christine; Beauregard, Hugues; Serri, Omar

2013-01-01

To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of <1.10, 2.65, and 5.36 μg/dL at 0, 30, and 60 minutes, respectively, confirming an adrenal insufficiency. Because the patient was unable to stop budesonide, she was advised to reduce the frequency of its administration and eventually taper the dose until cessation. Clinicians should be aware of the potential occurrence of iatrogenic Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

Delivery of inhaled drugs for infants and small children: a commentary on present and future needs.

PubMed

Fink, James B

2012-11-01

Although the manufacture of inhaled medications is a multibillion dollar industry, virtually no pharmaceutical drug/device combination has been approved for inhalation across the range of pediatric patient ages and sizes. The clinician who treats neonates, infants, or toddlers is often faced with the dilemma of prescribing inhaled medications that may be disease appropriate but have not been approved for use in patients in these age categories. Their use is thus technically "off label," with limited empirical data to guide both dose and device selection. This dilemma requires the prescribing physician to go beyond the limitations of the product label, often without benefit of appropriately designed clinical trials, in an attempt to select safe and effective doses for use with these smallest of patients. The vast majority of drugs approved for inhalation were studied by using aerosol devices designed for older children and adults using a mouthpiece interface, which may not be practical for use in infants and patients aged <4 years. The selection of the most age-appropriate device and interface is critical for the effective administration of the prescribed therapy. In the absence of industry-sponsored clinical trials in neonates, infants, and toddlers, in vitro and in vivo strategies may help guide age-appropriate dosing, device, and interface selection to better inform clinical practice. In this commentary, the challenges in developing and prescribing effective formulations for aerosol delivery across the range of pediatric ages and sizes are explored, with guidance for device and interface selection. Recommendations for future collaborative sharing of in vitro models and age-specific breathing patterns between academic and industry researchers could help regulators and clinicians better understand the impact age and size have on pulmonary drug delivery. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Outcome following inhalation anesthesia in birds at a veterinary referral hospital: 352 cases (2004-2014).

PubMed

Seamon, Amanda B; Hofmeister, Erik H; Divers, Stephen J

2017-10-01

OBJECTIVE To determine the outcome in birds undergoing inhalation anesthesia and identify patient or procedure variables associated with an increased likelihood of anesthesia-related death. DESIGN Retrospective case series. ANIMALS 352 birds that underwent inhalation anesthesia. PROCEDURES Medical records of birds that underwent inhalation anesthesia from January 1, 2004, through December 31, 2014, at a single veterinary referral hospital were reviewed. Data collected included date of visit, age, species, sex, type (pet, free ranging, or wild kept in captivity), body weight, body condition score, diagnosis, procedure, American Society of Anesthesiologists status, premedication used for anesthesia, drug for anesthetic induction, type of maintenance anesthesia, route and type of fluid administration, volumes of crystalloid and colloid fluids administered, intraoperative events, estimated blood loss, duration of anesthesia, surgery duration, recovery time, recovery notes, whether birds survived to hospital discharge, time of death, total cost of hospitalization, cost of anesthesia, and nadir and peak values for heart rate, end-tidal partial pressure of carbon dioxide, concentration of inhaled anesthetic, and body temperature. Comparisons were made between birds that did and did not survive to hospital discharge. RESULTS Of 352 birds, 303 (86%) were alive at hospital discharge, 12 (3.4%) died during anesthesia, 15 (4.3%) died in the intensive care unit after anesthesia, and 22 (6.3%) were euthanatized after anesthesia. Overall, none of the variables studied were associated with survival to hospital discharge versus not surviving to hospital discharge. CONCLUSIONS AND CLINICAL RELEVANCE Results confirmed previous findings that indicated birds have a high mortality rate during and after anesthesia, compared with mortality rates published for dogs and cats.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1997-12-31

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

[Packaging: the guarantee of medicinal quality].

PubMed

Chaumeil, J-C

2003-01-01

Primary packaging guarantees the pharmaceutical quality of the medicinal preparation received by the patient. Glass bottles containing parenteral solutions for example ensure that sterility, quality and optimal stability are preserved until administration. Recent innovations in materials research has lead to improvements in parenteral infusions. Multicompartmental bags, allowing extemporaneous mixtures without opening the container, constitute an extremely beneficial advance for the patient, allowing administration of mixtures with solutions and emulsions which would be unstable if stored. Metered dose pressurized inhalers are an excellent example of drug administration devices designed specifically to ensure quality and bioavailability. These examples illustrate the important role of primary packaging and demonstrate the usefulness of research and development in this area.

IRIS Toxicological Review of Formaldehyde (Interagency ...

EPA Pesticide Factsheets

On June 2, 2010, the Toxicological Review of Formaldehyde and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Formaldehyde and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Formaldehyde-Inhalation Assessment provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic inhalation exposure to formaldehyde.

Quantification of fatal helium exposure following self-administration.

PubMed

Malbranque, S; Mauillon, D; Turcant, A; Rouge-Maillart, C; Mangin, P; Varlet, V

2016-11-01

Helium is nontoxic at standard conditions, plays no biological role, and is found in trace amounts in human blood. Helium can be dangerous if inhaled to excess, since it is a simple tissue hypoxia and so displaces the oxygen needed for normal respiration. This report presents a fatal case of a middle-aged male victim who died from self-administered helium exposure. For the first time, the quantification of the helium levels in gastric and lung air and in blood samples was achieved using gas chromatography-mass spectrometry after airtight sampling. The results of the toxicological investigation showed that death was caused directly by helium exposure. However, based on the pathomorphological changes detected during the forensic autopsy, we suppose that the fatal outcome was the result of the lack of oxygen after inhalation.

The route and timing of hydrogen sulfide therapy critically impacts intestinal recovery following ischemia and reperfusion injury.

PubMed

Jensen, Amanda R; Drucker, Natalie A; Te Winkel, Jan P; Ferkowicz, Michael J; Markel, Troy A

2018-06-01

Hydrogen sulfide (H 2 S) has many beneficial properties and may serve as a novel treatment in patients suffering from intestinal ischemia-reperfusion injury (I/R). The purpose of this study was to examine the method of delivery and timing of administration of H 2 S for intestinal therapy during ischemic injury. We hypothesized that 1) route of administration of hydrogen sulfide would impact intestinal recovery following acute mesenteric ischemia and 2) preischemic H 2 S conditioning using the optimal mode of administration as determined above would provide superior protection compared to postischemic application. Male C57BL/6J mice underwent intestinal ischemia by temporary occlusion of the superior mesenteric artery. Following ischemia, animals were treated according to one of the following (N=6 per group): intraperitoneal or intravenous injection of GYY4137 (H 2 S-releasing donor, 50mg/kg in PBS), vehicle, inhalation of oxygen only, inhalation of 80ppm hydrogen sulfide gas. Following 24-h recovery, perfusion was assessed via laser Doppler imaging, and animals were euthanized. Perfusion and histology data were assessed, and terminal ileum samples were analyzed for cytokine production following ischemia. Once the optimal route of administration was determined, preischemic conditioning with H 2 S was undertaken using that route of administration. All data were analyzed using Mann-Whitney. P-values <0.05 were significant. Mesenteric perfusion following intestinal I/R was superior in mice treated with intraperitoneal (IP) GYY4137 (IP vehicle: 25.6±6.0 vs. IP GYY4137: 79.7±15.1; p=0.02) or intravenous (IV) GYY4137 (IV vehicle: 36.3±5.9 vs. IV GYY4137: 100.7±34.0; p=0.03). This benefit was not observed with inhaled H 2 S gas (O2 vehicle: 66.6±11.4 vs. H 2 S gas: 81.8±6.0; p=0.31). However, histological architecture was only preserved with intraperitoneal administration of GYY4127 (IP vehicle: 3.4±0.4 vs. IP GYY4137: 2±0.3; p=0.02). Additionally, IP GYY4137 allowed for significant attenuation of inflammatory chemokine production of IL-6, IP-10 and MIP-2. We then analyzed whether there was a difference between pre- and postischemic administration of IP GYY4137. We found that preconditioning of animals with intraperitoneal GYY4137 only added minor improvements in outcomes compared to postischemic application. Therapeutic benefits of H 2 S are superior with intraperitoneal application of an H 2 S donor compared to other administration routes. Additionally, while intraperitoneal treatment in both the pre- and postischemic period is beneficial, preischemic application of an H 2 S donor was found to be slightly better. Further studies are needed to examine long term outcomes and further mechanisms of action prior to widespread clinical application. Basic science. N/A. Copyright © 2018 Elsevier Inc. All rights reserved.

Superiority of PC-SOD to other anti-COPD drugs for elastase-induced emphysema and alteration in lung mechanics and respiratory function in mice.

PubMed

Tanaka, Ken-Ichiro; Sato, Keizo; Aoshiba, Kazutetsu; Azuma, Arata; Mizushima, Tohru

2012-06-15

Bronchodilators (such as ipratropium bromide), steroids (such as fluticasone propionate), and newly developed anti-inflammatory drugs (such as roflumilast) are used for patients with chronic obstructive pulmonary disease (COPD). We recently reported that lecithinized superoxide dismutase (PC-SOD) confers a protective effect in mouse models of COPD. We here examined the therapeutic effect of the combined administration of PC-SOD with ipratropium bromide on pulmonary emphysema and compared the effect of PC-SOD to other types of drugs. The severity of emphysema in mice was assessed by various criteria. Lung mechanics (elastance) and respiratory function (ratio of forced expiratory volume in the first 0.05 s to forced vital capacity) were assessed. Administration of PC-SOD by inhalation suppressed elastase-induced pulmonary emphysema, alteration of lung mechanics, and respiratory dysfunction. The concomitant intratracheal administration of ipratropium bromide did not alter the ameliorating effects of PC-SOD. Administration of ipratropium bromide, fluticasone propionate, or roflumilast alone did not suppress the elastase-induced increase in the pulmonary level of superoxide anion, pulmonary inflammatory response, pulmonary emphysema, alteration of lung mechanics, or respiratory dysfunction as effectively as did PC-SOD. PC-SOD, but not the other drugs, showed a therapeutic effect even when the drug was administered after the development of emphysema. PC-SOD also suppressed the cigarette smoke-induced pulmonary inflammatory response and increase in airway resistance. Based on these results, we consider that the inhalation of PC-SOD would be therapeutically beneficial for COPD.

Effect of toxic threat nerve agents on anesthetic requirements of representative pr-anesthetic medicants and inhalant and parenteral general anesthetic in the cat. Annual report, 15 July 1985-14 July 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, A.I.

1986-07-30

The effect of soman on anesthetic requirements of halothane and isoflurane was studied before and after administration of acepromazine maleate (0.2 mg/kg). Insufficient data has been obtained to date to draw conclusions on any possible drug interactions.

The effects of acute doses of nicotine on video lottery terminal gambling in daily smokers.

PubMed

McGrath, Daniel S; Barrett, Sean P; Stewart, Sherry H; Schmid, Evan A

2012-03-01

A growing body of evidence suggests that gambling frequently co-occurs with smoking, yet little is known about the degree to which nicotine and/or tobacco use influences gambling behavior. Nonetheless, an increasing number of studies suggest that acute administration of nicotine may alter other reinforcing behaviors in both animal and human models, raising the possibility that nicotine may also influence gambling behavior and craving. The purpose of this study was to examine the acute effects of nicotine on subjective and behavioral gambling responses. Twenty-eight (15 male) regular gamblers who smoke daily completed two double-blind laboratory sessions where their subjective and behavioral responses to video lottery terminal (VLT) gambling were assessed, following the administration of nicotine inhalers (NI; 4 mg deliverable) or placebo inhalers. NI significantly decreased tobacco-related cravings (p < 0.05) but did not affect gambling-related cravings, VLT betting patterns, or subjective responses (ps > 0.1). NI were found to acutely suppress tobacco-related cravings without influencing gambling. These results suggest that use of nicotine replacement therapies may be a safe option for gamblers who are attempting to quit smoking.

The Effectiveness of Aromatherapy for Depressive Symptoms: A Systematic Review.

PubMed

Sánchez-Vidaña, Dalinda Isabel; Ngai, Shirley Pui-Ching; He, Wanjia; Chow, Jason Ka-Wing; Lau, Benson Wui-Man; Tsang, Hector Wing-Hong

2017-01-01

Background . Depression is one of the greatest health concerns affecting 350 million people globally. Aromatherapy is a popular CAM intervention chosen by people with depression. Due to the growing popularity of aromatherapy for alleviating depressive symptoms, in-depth evaluation of the evidence-based clinical efficacy of aromatherapy is urgently needed. Purpose . This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients. Methods . A systematic database search was carried out using predefined search terms in 5 databases: AMED, CINHAL, CCRCT, MEDLINE, and PsycINFO. Outcome measures included scales measuring depressive symptoms levels. Results . Twelve randomized controlled trials were included and two administration methods for the aromatherapy intervention including inhaled aromatherapy (5 studies) and massage aromatherapy (7 studies) were identified. Seven studies showed improvement in depressive symptoms. Limitations . The quality of half of the studies included is low, and the administration protocols among the studies varied considerably. Different assessment tools were also employed among the studies. Conclusions . Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects. Particularly, aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy.

Devices for oral and respiratory paediatric medicines: What do healthcare professionals think?

PubMed

Walsh, Jennifer; Math, Marie-Christine; Breitkreutz, Jörg; Zerback, Thomas; Wachtel, Herbert

2015-08-15

Medical devices are crucial for the proper administration of paediatric medicines to children, but handling and dosing errors commonly appear in daily practice. As both the understanding and the usage of medical devices for oral and respiratory drug administration are heterogeneous among patients and caregivers, the European Paediatric Formulation Initiative (EuPFI) consortium performed a European survey among healthcare professional stakeholders in France, Germany, Hungary, Italy, Spain and UK. The results show country- and age-dependent usage of devices for oral administration of liquid formulations, with a clear preference for oral droppers and syringes in the neonatal phase and in early infancy. In older children, spoons and cups are more frequently used although it is recognized that they may fail in delivering correct doses. The percentage of medicinal products definitely requiring an oral administration device was estimated as 68.8% by the participants. The survey elaborated a similar usage pattern for medical devices for respiratory drug delivery: in young children drug solutions are nebulized, using face-masks and subsequently valved holding chambers or spacers, with increasing age metered-dose inhalers and later dry powder inhalers are preferably used. 56% of the responding healthcare professionals believed that providing an administration device helps to ensure that the patient receives the correct dose of medicine, and 41% agreed that patients must be given an administration device with each supply of medicine. Interestingly, 6.7% thought that patients tend not to use the device provided and remarkably 25.4% stated that patients already have a device. Although there is the highest count of treated children with device supply in Germany and Hungary, there are no observed significant differences in the six investigated European countries (p=0.057). Patient difficulties in correct oral and respiratory device use were identified by respondents and potential solutions discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions.

PubMed

Krämer, Irene; Schwabe, Astrid; Lichtinghagen, Ralf; Kamin, Wolfgang

2009-02-01

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of the nebulizer solution dornase alfa (Pulmozyme) with tobramycin nebulizer solutions (TOBI and GERNEBCIN 80 mg) are physico-chemically compatible. Drug combinations were prepared by mixing the content of one respule Pulmozyme with either one respule TOBI or one ampoule GERNEBCIN 80 mg. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity and tobramycin concentrations were determined by using a kinetic colorimetric DNase activity assay and a fluorescence immunoassay, respectively. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Tobramycin concentration was not affected by mixing the drug products. In spite of the high variability of the dornase alfa potency assay, it is obvious that activity is especially affected by sodium metabisulfite, used as excipient in GERNEBCIN. Patients should be advised, not to mix Pulmozyme with GERNEBCIN because of the incompatibility reaction. Further analytical studies are needed in order to determine the integrity and activity of dornase alfa in mixtures of Pulmozyme with TOBI. Finally clinical studies are necessary in order to demonstrate equivalent efficacy and safety of simultaneous inhalation in comparison to consecutive inhalation of both drugs. (c) 2008 Wiley-Liss, Inc.

The Effects of Inhalation Aromatherapy on Anxiety in Patients With Myocardial Infarction: A Randomized Clinical Trial

PubMed Central

Najafi, Zahra; Taghadosi, Mohsen; Sharifi, Khadijeh; Farrokhian, Alireza; Tagharrobi, Zahra

2014-01-01

Background: Anxiety is an important mental health problem in patients with cardiac disease. Anxiety reduces patients’ quality of life and increases the risk of different cardiac complications. Objectives: The aim of this study was to investigate the effects of inhalation aromatherapy on anxiety in patients with myocardial infarction. Patients and Methods: This was a randomized clinical trial conduced on 68 patients with myocardial infarction hospitalized in coronary care units of a large-scale teaching hospital affiliated to Kashan University of Medical Sciences, Kashan, Iran in 2013. By using the block randomization technique, patients were randomly assigned to experimental (33 patients receiving inhalation aromatherapy with lavender aroma twice a day for two subsequent days) and control (35 patients receiving routine care of study setting including no aromatherapy) groups. At the beginning of study and twenty minutes after each aromatherapy session, anxiety state of patients was assessed using the Spielberger’s State Anxiety Inventory. Data was analyzed using SPSS v. 16.0. We used Chi-square, Fisher’s exact, independent-samples T-test and repeated measures analysis of variance to analyze the study data. Results: The study groups did not differ significantly regarding baseline anxiety mean and demographic characteristics. However, after the administration of aromatherapy, anxiety mean in the experimental group was significantly lower than the control group. Conclusions: Inhalation aromatherapy with lavender aroma can reduce anxiety in patients with myocardial infarction. Consequently, healthcare providers, particularly nurses, can use this strategy to improve postmyocardial infarction anxiety management. PMID:25389481

Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site.

PubMed

Komatsu, H; Rawson, J; Barriga, A; Gonzalez, N; Mendez, D; Li, J; Omori, K; Kandeel, F; Mullen, Y

2018-04-01

Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Striatal dopamine dynamics in mice following acute and repeated toluene exposure.

PubMed

Apawu, Aaron K; Mathews, Tiffany A; Bowen, Scott E

2015-01-01

The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene's mechanism of action is unknown. The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry. Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene's locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25-50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice. These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.

KF19514, a phosphodieterase 4 and 1 inhibitor, inhibits PAF-induced lung inflammatory responses by inhaled administration in guinea pigs.

PubMed

Manabe, H; Akuta, K; Okamura, K; Ohmori, K

1997-12-01

Phosphodiesterase (PDE) 4 inhibitors are well known for their inhibitory effect on bronchoconstriction and inflammation and may be promising anti-asthma drugs. Platelet-activating factor (PAF) has been proposed as an inflammatory mediator to be relevant to asthma. It causes bronchoconstriction, airway microvascular leakage, inflammatory cell accumulation in the lung and hyperresponsiveness. In this study, we therefore have investigated the anti-asthmatic effects of the inhaled KF19514 [5-phenyl-3'-(3-pyridyl)methyl-3H-imidazo(4,5-c)(1,8) naphthyridin-4(5H)-one], a PDE 4 and 1 inhibitor, on PAF-induced lung inflammatory responses in guinea pigs. The inhaled KF19514 (0.0001-0.01%) significantly inhibited PAF-induced eosinophil and neutrophil accumulation into the airway and hyperresponsiveness in guinea pigs. The IC50 value of KF19514 against eosinophil accumulation was 14.8 microM (0.00063%). Moreover, the effect of KF19514 on the electrical field stimulation-induced bronchial contraction was examined using the main bronchi of guinea pigs in vitro. KF19514 inhibited both cholinergic and tachykininergic contraction and, in particular, produced a potent inhibitory effect on tachykininergic contraction (IC50 = 0.49 microM). The mechanism by which KF19514 inhibited the PAF-induced hyperresponsiveness may in part be the suppression of the tachykinin release. Based on these results, it was demonstrated that the inhaled KF19514 might have a significant potential effect on the inflammatory cell accumulation and hyperresponsiveness induced by PAF.

The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension.

PubMed

James, Adam T; Corcoran, John D; McNamara, Patrick J; Franklin, Orla; El-Khuffash, Afif F

2016-01-01

Milrinone may be an appropriate adjuvant therapy for infants with persistent pulmonary hypertension of the newborn. We aimed to describe the effect of milrinone administration on right and left ventricular function in infants with persistent pulmonary hypertension not responding to inhaled nitric oxide after 4 hours of administration. This is a retrospective review of infants born after or at 34 weeks of gestation with persistent pulmonary hypertension who received milrinone treatment. The primary endpoint was the effect of milrinone on myocardial performance and haemodynamics, including right and left ventricular outputs, tissue Doppler velocities, right ventricle and septal strain, and strain rate. Secondary endpoints examined included duration of inhaled nitric oxide and oxygen support. A total of 17 infants with a mean (standard deviation) gestation and birth weight of 39.8 (2.0) weeks and 3.45 (0.39) kilograms, respectively, were included in the study. The first echocardiogram was performed 15 hours after the commencement of nitric oxide inhalation. Milrinone treatment was started at a median time of 1 hour after the echocardiogram and was associated with an increase in left ventricular output (p=0.04), right ventricular output (p=0.004), right ventricle strain (p=0.01) and strain rate (p=0.002), and left ventricle s` (p<0.001) and a` (p=0.02) waves. There was a reduction in nitric oxide dose and oxygen requirement over the subsequent 72 hours (all p<0.05). The use of milrinone as an adjunct to nitric oxide is worth further exploration, with preliminary evidence suggesting an improvement in both oxygenation and myocardial performance in this group of infants.

Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia-reperfusion injury in rats.

PubMed

Yang, Y W; Cheng, W P; Lu, J K; Dong, X H; Wang, C B; Zhang, J; Zhao, L Y; Gao, Z F

2014-07-01

This study was designed to assess the neuroprotective effect of xenon-induced delayed postconditioning on spinal cord ischaemia-reperfusion injury (IRI) and to determine the time of administration for best neuroprotection in a rat model of spinal cord IRI. Fifty male rats were randomly divided equally into a sham group, control group, and three xenon postconditioning groups (n=10 per group). The control group underwent spinal cord IRI and immediately inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The three xenon postconditioning groups underwent the same surgical procedure and immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion or 1 and 2 h after reperfusion. The sham operation group underwent the same surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen. Neurological function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h of reperfusion. Histological examination was performed using Nissl staining and immunohistochemistry, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling staining. Compared with the control group, the three xenon postconditioning groups showed improvements in neurological outcomes, and had more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon-treated rats compared with controls. Xenon postconditioning up to 2 h after reperfusion provided protection against spinal cord IRI in rats, but the greatest neuroprotection occurred with administration of xenon for 1 h at reperfusion. © The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuroprotective, neurotherapeutic, and neurometabolic effects of carbon monoxide.

PubMed

Mahan, Vicki L

2012-12-27

Studies in animal models show that the primary mechanism by which heme-oxygenases impart beneficial effects is due to the gaseous molecule carbon monoxide (CO). Produced in humans mainly by the catabolism of heme by heme-oxygenase, CO is a neurotransmitter important for multiple neurologic functions and affects several intracellular pathways as a regulatory molecule. Exogenous administration of inhaled CO or carbon monoxide releasing molecules (CORM's) impart similar neurophysiological responses as the endogenous gas. Its' involvement in important neuronal functions suggests that regulation of CO synthesis and biochemical properties may be clinically relevant to neuroprotection and the key may be a change in metabolic substrate from glucose to lactate. Currently, the drug is under development as a therapeutic agent and safety studies in humans evaluating the safety and tolerability of inhaled doses of CO show no clinically important abnormalities, effects, or changes over time in laboratory safety variables. As an important therapeutic option, inhaled CO has entered clinical trials and its clinical role as a neuroprotective and neurotherapeutic agent has been suggested. In this article, we review the neuroprotective effects of endogenous CO and discuss exogenous CO as a neuroprotective and neurotherapeutic agent.

Dynamic CO₂ inhalation: a novel treatment for CSR-CSA associated with CHF.

PubMed

Wan, Zhi Hui; Wen, Fang Jing; Hu, Ke

2013-05-01

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is very common in patients with chronic congestive heart failure (CHF). A current concept of the key pathophysiological mechanism leading to CSR-CSA is a fluctuation of PaCO2 below and above the apneic threshold. A number of therapeutic approaches for CSR-CSA have been proposed-all with varying success, some of which include various modes of positive airway pressure among other strategies. However, CO2 oscillations seen in CSR-CSA have yet to be looked at as a specific therapeutic target by current treatments. Previous studies have shown that delivery of constant CO2 is efficacious in eliminating CSR-CSA by raising PaCO2, but there are serious concerns about the potential side effects, such as unwanted elevations in ventilation, work of breathing, and sympathetic nerve activity (SNA), and consequently CO2 inhalation therapy has not been recommended as a routine option for therapy. However, recent new studies into CO2 inhalation therapy have been made that may reshape its role as therapeutic. In this review, we will focus on the recent developments of administration of dynamic CO2 in the management of CSR-CSA in CHF patients.

Enhancement of suggestibility and imaginative ability with nitrous oxide.

PubMed

Whalley, M G; Brooks, G B

2009-05-01

Imaginative suggestibility, a trait closely related to hypnotic suggestibility, is modifiable under some circumstances. Nitrous oxide (laughing gas) is commonly used for sedation in dentistry and is reported to be more effective when combined with appropriate suggestions. The aim of this study was to determine whether nitrous oxide inhalation alters imaginative suggestibility and imagery vividness. Thirty participants were tested twice in a within-subjects design, once during inhalation of 25% nitrous oxide and once during inhalation of air plus oxygen. Before the study, participants' expectancies regarding the effects of nitrous oxide were assessed. Participants were blinded to drug administration. During each session, participants were verbally administered detailed measures of imagination and suggestibility: the Sheehan-Betts Quality of Mental Imagery scale and the Stanford Hypnotic Susceptibility Scale Form C, minus the hypnotic induction. Imaginative suggestibility and imaginative ability (imagery vividness) were both elevated in the nitrous oxide condition. This effect was unrelated to participants' expectations regarding the effects of the drug. Nitrous oxide increased imaginative suggestibility and imaginative ability. Possible explanations of these findings are discussed with respect to the effects of N-methyl-d-aspartate antagonists and to other pharmacological effects upon suggestibility and imagination.

Inhalation exposure to methylene chloride does not induce systemic immunotoxicity in rats.

PubMed

Warbrick, E V; Kilgour, J D; Dearman, R J; Kimber, I; Dugard, P H

2003-07-11

Methylene chloride (dichloromethane) is used in a variety of industrial applications. To date, there has been no formal assessment of immunotoxicity attributed to methylene chloride. Studies were undertaken to examine whether methylene chloride has any potential to influence the integrity of immune function. For this purpose, Sprague-Dawley rats of both genders were exposed by inhalation to a single high dose (5000 ppm) of methylene chloride for 6 h/d, 5 d/wk for 28 d. This was considered the relevant route of administration, as not only is inhalation a primary route for human exposure to methylene chloride, but, also, the chemical is absorbed rapidly via the lungs. Under these conditions of exposure, methylene chloride failed to influence absolute or relative thymus weights in either gender and produced a significant reduction in relative, but not absolute, spleen weight in female rats only. Immunocompetence was measured as a function of the ability of treated animals to mount immunoglobulin M (IgM) antibody responses to sheep red blood cells (SRBC) as determined by enzyme-linked immunosorbent assay (ELISA). Exposure to methylene chloride did not affect antibody production. Evidence indicates that under these conditions of exposure, methylene chloride did not compromise immune function.

Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans.

PubMed

Nagy, Christa F; Leach, Timothy S; King, Alex; Guttendorf, Robert

2017-11-10

Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6-9 days, and terminal half-life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection-site abscesses or hypersensitivity reactions occurred; no subjects developed treatment-emergent antitherapeutic antibodies over the study period of 71 days. © 2017, The American College of Clinical Pharmacology.

Inhaled Insulin: A Clinical and Historical Review.

PubMed

Chan, Jason; Cheng-Lai, Angela

Insulin is the most effective blood glucose lowering agent and remains one of the cornerstones of diabetes management. However, many individuals with diabetes are either reluctant to initiate or are nonadherent to their insulin therapy for various reasons, including fear of frequent injections. Technosphere Insulin (TI) is a novel inhaled insulin powder that is approved by the United States Food and Drug Administration for the management of diabetes. The results from 2 phase III clinical trials have shown that TI was noninferior to subcutaneous insulin aspart and superior to inhaled placebo in lowering HbA1c in patients with diabetes mellitus types 1 and 2, respectively. Across both studies, TI appears to be generally well tolerated, with the most common adverse events being hypoglycemia and cough. However, long-term pulmonary safety concerns have not been addressed and additional studies are needed. Overall, TI appears to be a promising noninvasive prandial insulin alternative for individuals with diabetes who are at risk for medication nonadherence due to aversion to frequent injections. This article provides a review of the historical development of TI, its safety and efficacy data, and its advantages and disadvantages over traditional injectable insulins.

The role of leukotrienes in airway inflammation.

PubMed

Ogawa, Yoshiko; Calhoun, William J

2006-10-01

Cysteinyl leukotrienes (cysLTs) are a class of closely structurally related lipid molecules, originally described as slow-reacting substance of anaphylaxis, with a myriad of biologic functions. These activities include producing smooth muscle contraction and mucus secretion, recruiting allergic inflammatory cells, modulating cytokine production, influencing neural transmission, and altering structural changes in the airway. Administration of cysLTs to animals and human subjects reproduces many features of allergic inflammation and asthma. Leukotriene (LT) blockers have independent efficacy in asthma and improve pulmonary function when added to inhaled steroids. Conversely, blockade of this pathway both in animals and in human subjects results in important reductions in inflammation and its consequences and might reduce structural changes of remodeling. These data collectively make a compelling case for an important role of cysLTs in airway inflammation and asthma. However, the magnitude of effect of anti-LTs is smaller than that of corticosteroids, and there is more variability in benefit of LT blockade than is seen with inhaled steroids. In addition, adding anti-LTs to inhaled steroids in asthmatic patients does not appear to produce added anti-inflammatory benefit. Genetic polymorphisms and environmental factors, such as tobacco smoke exposure, might underlie some of the heterogeneity of response to LT blockers.

Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Critchley, J.A.J.H.; Beeley, J.M.; Clark, R.J.

1990-04-01

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. The authors evaluated NAC and methylprednisolone in two rats models of inhalation injury: 40-hr exposure to >97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). Themore » increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. They caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.« less

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 the trials demonstrated that IB/FEN via Respimat SMI allows a reduction in the nominal dose of IB/FEN, while offering similar therapeutic efficacy and safety to a CFC-MDI. In children, Respimat SMI obviates the need for a spacer.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

PubMed

Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

2017-05-01

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of drugs are deposited in the oral cavity. Hence, the output of a modified DPI has been evaluated to achieve improved drug delivery, especially needed when targeting the smaller lung airways. This study is the first to utilize CF-PD methodology to simulate drug-aerosol transport and deposition under actual breathing conditions in a whole lung model, using a commercial dry-powder inhaler for realistic inlet conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

PubMed

Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

2003-05-01

The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC(50) methods. In order to cope with rather narrow dose/concentration classes of the GHS we have, as in our previous publications, combined the outcome of all results that can be obtained during testing for the allocation to one of the defined toxicity classes of the GHS. Our results strongly recommend the deletion of the dermal LD(50) and the inhalation LC(50) test as regulatory tests and the adoption of the dermal and inhalation ATC methods as internationally accepted alternatives.

[Pharmacological action and clinical aspects of salmeterol].

PubMed

Oguri, Kojiro

2003-09-01

Previous systemic beta(2) agonists such as procatrol tablets and tulobuterol patch were developed in Japan to address nocturnal symptoms and maintenance of lung function in asthmatic patients. Salmeterol, a potent and highly selective in beta(2) adrenocepter agonist with a duration of action greater than 12 h, was developed to provide long duration of bronchodilation with binding to a non-active site in the beta(2)-adrenocepter. Salmeterol is administrated via dry power inhalation and clinical studies have showed it has a good efficacy and a good safety profile, similar to inhaled steroids. Indeed, many clinical studies showed that salmeterol demonstrated better efficacy than long-acting beta(2)-agonist oral bronchodilators, theophyllines, and leukotriene-receptor antagonists in asthmatic patients and anticholinergic agents and theophyllines in COPD patients. Salmeterol will provide clinical benefits for Japanese asthma and COPD patients.

Appetite-enhancing effects of vanilla flavours such as vanillin.

PubMed

Ogawa, Kakuyou; Tashima, Akira; Sadakata, Momoko; Morinaga, Osamu

2018-06-01

Vanilla flavour is familiar to consumers through foods, cosmetics, household products and some medicines. Vanilla flavouring agents typically contain vanillin or its analogue ethyl vanillin. Our previous study revealed that the inhalation of eugenol, which contains a vanillyl group, has an appetite-enhancing effect, and the inhalation of aroma compounds containing the vanillyl group or its analogues led to increased food intake in mice. Here, we found that vanillin, ethyl vanillin and eugenol showed appetite-enhancing effects, whereas isoeugenol and safrole did not. These results suggest that the appetite-enhancing effects could be attributable to the vanillyl group and could be affected by the position of the double bond in the aliphatic chain. Furthermore, the results of intraperitoneal administration of eugenol and vanillin suggest that their appetite-enhancing effects could occur via stimulation of olfactory receptors.

Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax.

PubMed

Yamamoto, Brent J; Shadiack, Annette M; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S; Serbina, Natalya V

2016-10-01

The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. Copyright © 2016 Yamamoto et al.

Obiltoxaximab Prevents Disseminated Bacillus anthracis Infection and Improves Survival during Pre- and Postexposure Prophylaxis in Animal Models of Inhalational Anthrax

PubMed Central

Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; Gonzales, Nestor; O'Connor, Edward; Casey, Leslie S.

2016-01-01

The Centers for Disease Control and Prevention recommend adjunctive antitoxins when systemic anthrax is suspected. Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. The impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indication are presented here. New Zealand White rabbits and cynomolgus macaques received obiltoxaximab as a single intramuscular or intravenous dose of 2 to 16 mg/kg of body weight at various times relative to Bacillus anthracis aerosol spore challenge. The primary endpoint was survival, and effect of treatment timing was explored. In rabbits, obiltoxaximab administration 9 h postchallenge singly or combined with a 5-day levofloxacin regimen protected 89% to 100% of animals compared to 33% with levofloxacin monotherapy. In cynomolgus macaques, a single intramuscular dose of 16 mg/kg obiltoxaximab led to 100% survival when given 1 to 3 days preexposure and 83% to 100% survival when given 18 to 24 h postexposure and prior to systemic bacteremia onset. Obiltoxaximab administration after bacteremia onset resulted in lower (25% to 50%) survival rates reflective of treatment setting. Prophylactic administration of obiltoxaximab before spore challenge or to spore-challenged animals before systemic bacterial dissemination is efficacious in promoting survival, ameliorating toxemia, and inhibiting bacterial spread to the periphery. PMID:27431219

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.

Cardiopulmonary effects of administration of a combination solution of xylazine, guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated calves.

PubMed

Kerr, Carolyn L; Windeyer, Claire; Bouré, Ludovic P; Mirakhur, Kuldip K; McDonell, Wayne

2007-12-01

To compare the cardiopulmonary effects of administration of a solution of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in mechanically ventilated calves undergoing surgery. 13 male calves 2 to 26 days of age. Procedures-In calves in the XGK group, anesthesia was induced (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the isoflurane group, anesthesia was induced and maintained with isoflurane in oxygen. The rates of XGK infusion and isoflurane administration were adjusted to achieve suitable anesthetic depth. All calves received 100% oxygen and were mechanically ventilated to maintain end-tidal carbon dioxide concentrations from 35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal approach. Cardiopulmonary variables were measured before induction and at intervals up to 90 minutes after anesthetic induction. The quality of induction was excellent in all calves. The XGK requirements were 0.57 +/- 0.18 mL/kg and 2.70 +/- 0.40 mL/kg/h to induce and maintain anesthesia, respectively. Heart rate was significantly lower than baseline throughout the anesthetic period in the XGK group. Systolic arterial blood pressure was significantly higher in the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac index was lower than baseline in both groups. Differences between groups in cardiac index and arterial blood gas values were not significant. Administration of XGK resulted in excellent anesthetic induction and maintenance with cardiopulmonary alterations similar to those associated with isoflurane in mechanically ventilated calves.

Effect of formoterol/budesonide combination on arterial blood gases in patients with acute exacerbation of COPD.

PubMed

Cazzola, M; Noschese, P; De Michele, F; D'Amato, G; Matera, M G

2006-02-01

Patients with severe chronic airway obstruction might suffer dangerous hypoxemia after administration of a beta-agonist despite bronchodilation. We first compared the acute effects on gas exchange of two doses of formoterol Turbuhaler (9 and 18 microg) in 10 patients with acute exacerbation of COPD. Afterwards, we compared the acute effects of formoterol Turbuhaler 9 microug with those of formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg in 10 other patients with acute exacerbation of COPD. Finally, we compared the changes in PaO(2) induced by formoterol Turbuhaler 9 microg or formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg with those in FEV(1) in 10 other patients with acute exacerbation of COPD. Each agent was given on separate days, and the patients' arterial blood gases were measured at baseline and at intervals of 120 min. Small but statistically significant declines in PaO(2) were found after administration of both formoterol 9 and 18 microg. In the second group of patients, formoterol 9 microg alone again induced a significant decrease in PaO(2). However, the simultaneous administration of budesonide 320 microg significantly reduced the acute effect of formoterol on PaO(2). In a third group of 10 patients we confirmed a small but significant decrease in PaO(2) after formoterol alone and the reduction of this effect when budesonide was administered simultaneously. Moreover, we also documented that addition of budesonide amplified the fast onset of action of formoterol. These results suggest that when treating patients suffering from acute exacerbation of COPD with formoterol, it is prudent to check their arterial blood gases. In any case, combined administration of formoterol and budesonide reduces the potential for acute effects of formoterol on blood-gas tensions.

Complete healing of chronic wounds of a lower leg with haemoglobin spray and regeneration of an accompanying severe dermatoliposclerosis with intermittent normobaric oxygen inhalation (INBOI): a case report

PubMed Central

Barnikol, Wolfgang K. R.; Pötzschke, Harald

2011-01-01

A new healing procedure has been developed on the basis of the successful treatment of therapy-resistant hypoxic (and practically anoxic) leg ulcerations located within a heavy dermatoliposclerosis. The procedure involves an initial intra-ulceral application of haemoglobin followed by the intermittent administration of normobaric oxygen via inhalation. Haemoglobin is capable of externally supplying the granulating wound bed with oxygen at low partial pressure in a physiological manner, like a micro lung, so that oxidative stress can be avoided. A long-term daily administration of oxygen from within – including the peri-ulceral skin – is achieved by intermittent normobaric oxygen inhalation (INBOI) regularly throughout the day in the form of 1-hour sessions. Using this combined healing treatment during haemoglobin applications the ulcerations healed within about 1 month, and subsequently with INBOI therapy within further approx. 4 months the peri-ulceral skin regenerated as far as the oxygenation status was concerned: The peri-ulceral transcutaneous oxygen partial pressure (tcPO2) of zero (measured during breathing of normal air) rose to a satisfactory value of approx. 35 mmHg. After 28 months of treatment, the completely hypoxic and degenerated skin on the leg had practically returned to normal with a PO2 of 45 mmHg. Furthermore, the skin dermatoliposclerosis regressed. The skin regeneration was long-lasting, which was probably related to cellular tissue regeneration with an increase in the capillary density, whereby it had to be maintained by regular oxygen inhalation (INBOI maintaining treatment). By unintended intra-individual therapy variations it is evidenced that local hypoxia was the reason for skin degeneration: 3 x 1 h oxygen inhalation were sufficient for the healing treatment; 2 x 1 h sufficed for maintenance, whereas 2 x 0.5 h did not. The new procedure carries practically no risks, is simple, cheap and effective. Whereas the application of haemoglobin requires professional supervision, the oxygen inhalation can be carried out at home following initial guidance and monitoring by a physician. Using this novel method, the therapy-resistant ulceration could be closed within 5 months, during which daily outpatient care was only necessary for 1 month. The successful outcome of the treatment in terms of improvement of oxygen supply can monitored at any time using peri-ulceral tcPO2 measurements, whereby, due to the inhomogeneity of the values, measurements at a minimum of two locations at the wound edge are strongly recommended and more measurements at more skin locations would be preferable. Besides its use in the healing of ulcers, the new procedure is also suitable for the prevention of ulceration development (prophylactic INBOI treatment) in skin rendered susceptible due to the presence of hypoxia. Here, peri-ulceral transcutaneous oxygen partial pressures of below 10 mmHg should be considered as being critical and are an indication for a prophylactic oxygen inhalation treatment. The new procedure may also be suitable even before the peri-ulceral oxygen partial pressure falls below 10 mmHg. Four measures for rehabilitation, conservation, and prevention with regard to a healed chronic wound are proposed. PMID:21468328

Effect of prewarming on the body temperature of small dogs undergoing inhalation anesthesia.

PubMed

Rigotti, Clara F; Jolliffe, Colette T; Leece, Elizabeth A

2015-10-01

To investigate whether prewarming affects body temperature of small dogs (weighing < 10 kg [22 lb]) undergoing inhalation anesthesia. Prospective, randomized, blinded clinical trial. Animals: 20 dogs weighing < 10 kg with American Society of Anesthesiologists physical status I or II. Baseline rectal temperature was recorded. Before IM administration of buprenorphine hydrochloride and acepromazine maleate, dogs were randomly assigned to be placed in a pediatric incubator at 33°C (91.4°F) for approximately 30 to 60 minutes (prewarming group) or to receive no prewarming (control group); subsequently, dogs underwent inhalation anesthesia with isoflurane in oxygen. Rectal, esophageal, and ambient temperatures were measured every 5 minutes from induction of anesthesia (IOA) for > 1 hour by an observer who was unaware of treatment. If a dog became hypothermic (esophageal temperature < 36°C [96.8°F]), it was withdrawn from the study. Variables of interest relating to dogs, anesthesia, temperatures, hypothermia, and study withdrawal were compared between groups. 1 dog was excluded from the prewarming group after becoming excessively excited in the incubator. Between groups, age, weight, body condition score, degree of preanesthesia sedation, interval from sedation to IOA, duration of anesthesia, baseline rectal temperature, rectal temperatures immediately prior to IOA, esophageal temperature following IOA, ambient temperature during the first 70 minutes of anesthesia, esophageal or rectal temperature during the first 90 minutes of anesthesia, and incidence of hypothermia and study withdrawal (5 dogs/group) did not differ significantly. Prewarming in an incubator prior to IOA failed to improve or maintain body temperature of dogs weighing < 10 kg during inhalation anesthesia.

Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

PubMed

Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; de Moraes, Natália Valadares; Lepera, José Salvador

2015-10-01

Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-∞)) was calculated using the Gauss-Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-∞) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-resolution 3D MR microangiography of the rat ocular circulation.

PubMed

Shih, Yen-Yu I; Muir, Eric R; Li, Guang; De La Garza, Bryan H; Duong, Timothy Q

2012-07-01

To develop high-spatial-resolution magnetic resonance (MR) microangiography techniques to image the rat ocular circulation. Animal experiments were performed with institutional Animal Care Committee approval. MR microangiography (resolution, 84×84×84 μm or 42×42×84 μm) of the rat eye (eight rats) was performed by using a custom-made small circular surface coil with an 11.7-T MR unit before and after monocrystalline iron oxide nanoparticle (MION) injection. MR microangiography measurements were made during air, oxygen, and carbogen inhalation. From three-dimensional MR microangiography, the retina was virtually flattened to enable en face views of various retinal depths, including the retinal and choroidal vascular layers. Signal intensity changes within the retinal or choroidal arteries and veins associated with gas challenges were analyzed. Statistical analysis was performed by using paired t tests, with P<.05 considered to indicate a significant difference. Bonferroni correction was used to adjust for multiple comparisons. The central retinal artery, long posterior ciliary arteries, and choroidal vasculature could be distinguished on MR microangiograms of the eye. With MR microangiography, retinal arteries and veins could be distinguished on the basis of blood oxygen level-dependent contrast. Carbogen inhalation-enhanced MR microangiography signal intensity in both the retina (P=.001) and choroid (P=.027) compared with oxygen inhalation. Carbogen inhalation showed significantly higher signal intensity changes in the retinal arteries (P=.001, compared with oxygen inhalation), but not in the veins (P=.549). With MION administration, MR microangiography depicted retinal arterial vasoconstriction when the animals were breathing oxygen (P=.02, compared with animals breathing air). MR microangiography of the eye allows depth-resolved imaging of small angiographic details of the ocular circulation. This approach may prove useful in studying microvascular pathologic findings and neurovascular dysfunction in the eye and retina. © RSNA, 2012.

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study.

PubMed

Barnestein-Fonseca, Pilar; Leiva-Fernández, José; Vidal-España, Francisca; García-Ruiz, Antonio; Prados-Torres, Daniel; Leiva-Fernández, Francisca

2011-02-14

Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients. A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group. Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context. Current Controlled Trials ISRCTN18841601.

mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma following multi-walled carbon nanotube inhalation exposure in mice

PubMed Central

Snyder-Talkington, Brandi N.; Dong, Chunlin; Sargent, Linda M.; Porter, Dale W.; Staska, Lauren M.; Hubbs, Ann F.; Raese, Rebecca; McKinney, Walter; Chen, Bean T.; Battelli, Lori; Lowry, David T.; Reynolds, Steven H.; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2015-01-01

Inhalation exposure to multi-walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis, and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma. Six-week-old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA-damaging agent methylcholanthrene (MCA, 10 μg/g body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (control) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR-122-5p in the presence of hyperplasia, mthfd2 and miR-206-3p in the presence of fibrosis, fam178a and miR-130a-3p in the presence of bronchiolo-alveolar adenoma, and il7r and miR-210-3p in the presence of bronchiolo-alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT-induced lung pathological changes. PMID:25926378

[Sedation with 50 % nitrous oxide/oxygen in paediatric dentistry].

PubMed

Atash, R; Vanden Abbeele, A

2008-09-01

The management of paediatric dentistry treatment is essentially based on behaviour management but some behaviour troubles or mental retardation may hinder this kind of treatment at the dental office without any premedication. This often leads the dentist to change his treatment planning even if this may compromise the quality of treatment . Conscious sedation techniques enable stress and pain control during the active treatment phase and represent a useful alternative to general anaesthesia which cannot be used on a routine based level. Conscious sedation by the inhalation of nitrous oxide and oxygen (MEOPA) represents a good choice, as well as by its harmlessness as by its fast reversibility. MEOPA is a precious help in our practice, provided that its administration is totally under central and all contra-indication are respected. However sedation by inhalation should in no case be systematized and its goal must remain the progressive rehabilitation of the patient in a circuit of traditional ambulatory care.

Ultrasonically-Induced Cavitation In Vivo Depends on the Physiological State

NASA Astrophysics Data System (ADS)

Vykhodtseva, Natalia I.; Kondrashova, Maria N.

2006-05-01

Purpose: To test the hypothesis that the ultrasound-induced cavitation can be facilitated by excitation and stress. Methods: Acoustic emission was monitored from the region of the femoral artery of non-anesthetized rats using a resonant focusing detector (RFD). The RFD consists of two transducers: an inner transmitting transducer (0.87 MHz, R/D=70/28mm), an annular receiving transducer (0.43 MHz, R=70 mm, Dint/Dext=37 /58 mm). Acoustical emission was monitored: (1) during mild immobilization stress (MIS); (2) after strong immobilization stress (SIS); (3) after succinic acid administration (SUC); (4) during negative air-ion inhalation (NAI). Results: The subharmonic emission varied as a function of the physiological states. Both strong immobilization stress and SUC, which increases adrenaline release and stimulates physiological activity of cells, increased cavitation activity. Inhalation of NAI abolished stress-induced cavitation providing a sedative effect.

Pacific Northwest Laboratory annual report for 1976 to the ERDA Assistant Administrator for Environment and Safety. Part 1. Biomedical Sciences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, R.C.

1977-05-01

Separate abstracts were prepared for individual sections of this publication. In addition to research reports the publication also contains organization charts, author index, and appendixes showing data on selected parameters relative to life-span dose-effect studies with inhaled /sup 239/PuO/sub 2/, /sup 238/PuO/sub 2/, and /sup 239/Pu in beagles. (HLW)

Biomedical Effects of Chemical-Threat-Agent Antidote and Pretreatment Drugs. An Abstracted Bibliography. Volume 1.

DTIC Science & Technology

1986-04-01

Adams, R., Venna, P., Jackson, A., and Miller, R. TITLE: Plasma pharmacokinetics of intravenously administered atropine in normal human subjects Journal...atropine by i.v. route and inhalation. Measurements of respiratory airway resistance, N2 closing volume, maximal expiratory flow volume, pressure volume...maximum flow -static recoil and esophageal elasticity were compared to non-atropinized values. FINDINGS: "I.V. administration produced a marked

Medical use of cannabis in the Netherlands.

PubMed

Gorter, Robert W; Butorac, Mario; Cobian, Eloy Pulido; van der Sluis, Willem

2005-03-08

The authors investigated the indications for cannabis prescription in the Netherlands and assessed its efficacy and side effects. A majority (64.1%) of patients reported a good or excellent effect on their symptoms. Of these patients, approximately 44% used cannabis for >/=5 months. Indications were neurologic disorders, pain, musculoskeletal disorders, and cancer anorexia/cachexia. Inhaled cannabis was perceived as more effective than oral administration. Reported side effects were generally mild.

Electrical Connection of Enzyme Redox Centers to Electrodes

DTIC Science & Technology

1992-03-20

concentration in the target organ or the affected physiological function ; and a microcontroller or microprocessor calculating the dose and timing the delivery...followed by introduction of medical feedback loops will allow the pharmaceutical industry to expand its range of drug delivery methods. Today’s primary ...inhalation (derived of the large lung surface area) and continuous, non -invasive administration, in the case of iontophoresis. The use of these

The Effectiveness of Aromatherapy for Depressive Symptoms: A Systematic Review

PubMed Central

Ngai, Shirley Pui-Ching; He, Wanjia; Chow, Jason Ka-Wing; Tsang, Hector Wing-Hong

2017-01-01

Background. Depression is one of the greatest health concerns affecting 350 million people globally. Aromatherapy is a popular CAM intervention chosen by people with depression. Due to the growing popularity of aromatherapy for alleviating depressive symptoms, in-depth evaluation of the evidence-based clinical efficacy of aromatherapy is urgently needed. Purpose. This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients. Methods. A systematic database search was carried out using predefined search terms in 5 databases: AMED, CINHAL, CCRCT, MEDLINE, and PsycINFO. Outcome measures included scales measuring depressive symptoms levels. Results. Twelve randomized controlled trials were included and two administration methods for the aromatherapy intervention including inhaled aromatherapy (5 studies) and massage aromatherapy (7 studies) were identified. Seven studies showed improvement in depressive symptoms. Limitations. The quality of half of the studies included is low, and the administration protocols among the studies varied considerably. Different assessment tools were also employed among the studies. Conclusions. Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects. Particularly, aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy. PMID:28133489

Estimating Supplies Program: Evaluation Report

DTIC Science & Technology

2002-12-24

Inhalation, Non-vaccinated1, Incubating, Asymptomatic 352 Anthrax, Inhalation, Non-vaccinated, Prodromal 353 Anthrax, Inhalation, Non-vaccinated, Acute...B-11 PC Code PC Description 354 Anthrax, Inhalation, Vaccinated, Asymptomatic 355 Anthrax, Inhalation, Vaccinated, Prodromal 356...Anthrax, Inhalation, Vaccinated, Acute 357 Plague, Inhalation, Incubating, Asymptomatic 358 Plague, Inhalation, Acute 359 Plague Meningitis 360

Humidification and heating of inhaled gas in patients with artificial airway. A narrative review

PubMed Central

Plotnikow, Gustavo Adrián; Accoce, Matias; Navarro, Emiliano; Tiribelli, Norberto

2018-01-01

Instrumentation of the airways in critical patients (endotracheal tube or tracheostomy cannula) prevents them from performing their function of humidify and heating the inhaled gas. In addition, the administration of cold and dry medical gases and the high flows that patients experience during invasive and non-invasive mechanical ventilation generate an even worse condition. For this reason, a device for gas conditioning is needed, even in short-term treatments, to avoid potential damage to the structure and function of the respiratory epithelium. In the field of intensive therapy, the use of heat and moisture exchangers is common for this purpose, as is the use of active humidification systems. Acquiring knowledge about technical specifications and the advantages and disadvantages of each device is needed for proper use since the conditioning of inspired gases is a key intervention in patients with artificial airway and has become routine care. Incorrect selection or inappropriate configuration of a device can have a negative impact on clinical outcomes. The members of the Capítulo de Kinesiología Intensivista of the Sociedad Argentina de Terapia Intensiva conducted a narrative review aiming to show the available evidence regarding conditioning of inhaled gas in patients with artificial airways, going into detail on concepts related to the working principles of each one. PMID:29742220

Humidification and heating of inhaled gas in patients with artificial airway. A narrative review.

PubMed

Plotnikow, Gustavo Adrián; Accoce, Matias; Navarro, Emiliano; Tiribelli, Norberto

2018-03-01

Instrumentation of the airways in critical patients (endotracheal tube or tracheostomy cannula) prevents them from performing their function of humidify and heating the inhaled gas. In addition, the administration of cold and dry medical gases and the high flows that patients experience during invasive and non-invasive mechanical ventilation generate an even worse condition. For this reason, a device for gas conditioning is needed, even in short-term treatments, to avoid potential damage to the structure and function of the respiratory epithelium. In the field of intensive therapy, the use of heat and moisture exchangers is common for this purpose, as is the use of active humidification systems. Acquiring knowledge about technical specifications and the advantages and disadvantages of each device is needed for proper use since the conditioning of inspired gases is a key intervention in patients with artificial airway and has become routine care. Incorrect selection or inappropriate configuration of a device can have a negative impact on clinical outcomes. The members of the Capítulo de Kinesiología Intensivista of the Sociedad Argentina de Terapia Intensiva conducted a narrative review aiming to show the available evidence regarding conditioning of inhaled gas in patients with artificial airways, going into detail on concepts related to the working principles of each one.

Xenon Impairs Reconsolidation of Fear Memories in a Rat Model of Post-Traumatic Stress Disorder (PTSD)

PubMed Central

Meloni, Edward G.; Gillis, Timothy E.; Manoukian, Jasmine; Kaufman, Marc J.

2014-01-01

Xenon (Xe) is a noble gas that has been developed for use in people as an inhalational anesthestic and a diagnostic imaging agent. Xe inhibits glutamatergic N-methyl-D-aspartate (NMDA) receptors involved in learning and memory and can affect synaptic plasticity in the amygdala and hippocampus, two brain areas known to play a role in fear conditioning models of post-traumatic stress disorder (PTSD). Because glutamate receptors also have been shown to play a role in fear memory reconsolidation – a state in which recalled memories become susceptible to modification – we examined whether Xe administered after fear memory reactivation could affect subsequent expression of fear-like behavior (freezing) in rats. Male Sprague-Dawley rats were trained for contextual and cued fear conditioning and the effects of inhaled Xe (25%, 1 hr) on fear memory reconsolidation were tested using conditioned freezing measured days or weeks after reactivation/Xe administration. Xe administration immediately after fear memory reactivation significantly reduced conditioned freezing when tested 48 h, 96 h or 18 d after reactivation/Xe administration. Xe did not affect freezing when treatment was delayed until 2 h after reactivation or when administered in the absence of fear memory reactivation. These data suggest that Xe substantially and persistently inhibits memory reconsolidation in a reactivation and time-dependent manner, that it could be used as a new research tool to characterize reconsolidation and other memory processes, and that it could be developed to treat people with PTSD and other disorders related to emotional memory. PMID:25162644

Inhaled Epoprostenol Through Noninvasive Routes of Ventilator Support Systems.

PubMed

Ammar, Mahmoud A; Sasidhar, Madhu; Lam, Simon W

2018-06-01

The administration of inhaled epoprostenol (iEPO) through noninvasive routes of ventilator support systems has never been previously evaluated. Describe the use of iEPO when administered through noninvasive routes of ventilator support systems. Critically ill patients admitted to the intensive care unit who received iEPO through noninvasive routes were analyzed. Improvements in respiratory status and hemodynamic parameters were evaluated. Safety end points assessed included hypotension, rebound hypoxemia, significant bleeding, and thrombocytopenia. A total of 36 patients received iEPO through noninvasive routes: high-flow oxygen therapy through nasal cannula, n = 29 (81%) and noninvasive positive-pressure ventilation, n = 7 (19%). Sixteen patients had improvement in their respiratory status: mean decrease in fraction of inspired oxygen (FiO 2 ), 20% ± 13%; mean increase in partial pressure of arterial oxygen to FiO 2 (PaO 2 /FiO 2 ) ratio, 60 ± 50 mm Hg; and mean decrease in HFNC oxygen flow rate, 6 ± 3 liters per minute (LPM). Eight patients had declines in their respiratory status (mean increase in FiO 2 , 30% ± 20%; mean decrease in PaO 2 /FiO 2 ratio, 38 ± 20 mm Hg; and mean increase in HFNC oxygen flow rate, 15 ± 10 LPM), and 12 patients had no change in their respiratory status. Conclusion and Relevance: This represents the first evaluation of the administration of iEPO through noninvasive routes of ventilator support systems and demonstrates that in critically ill patients, iEPO could be administered through a noninvasive route. Further evaluation is needed to determine the extent of benefit with this route of administration.

Studies of Chlordane Availability and Volatility in Air Force Soils and Facilities

DTIC Science & Technology

2011-03-01

exposure, or inhalation of vapors. Chlordane primarily affects the nervous system and the digestive system causing headaches, irritability, confusion and...Administration (FDA) limits chlordane in fruits and vegetables to  ppb, and  ppb in animal fat and fish (ATSDR 1994). Exposure in the...roots of poplar and willow trees was a potentially useful tool for removing the pesticide from groundwater (Skaates et al. 2005). The potential of fungi

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence.

PubMed

Taylor, Terence E; Lacalle Muls, Helena; Costello, Richard W; Reilly, Richard B

2018-01-01

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be clinically beneficial for inhaler technique training and the remote monitoring of patient adherence.

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

PubMed Central

Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

2018-01-01

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be clinically beneficial for inhaler technique training and the remote monitoring of patient adherence. PMID:29346430

The inhalation characteristics of patients when they use different dry powder inhalers.

PubMed

Azouz, Wahida; Chetcuti, Philip; Hosker, Harold S R; Saralaya, Dinesh; Stephenson, John; Chrystyn, Henry

2015-02-01

The characteristics of each inhalation maneuver when patients use dry powder inhalers (DPIs) are important, because they control the quality of the emitted dose. We have measured the inhalation profiles of asthmatic children [CHILD; n=16, mean forced expiratory volume in 1 sec (FEV1) 79% predicted], asthmatic adults (ADULT; n=53, mean predicted FEV1 72%), and chronic obstructive pulmonary disease (COPD; n=29, mean predicted FEV1 42%) patients when they inhaled through an Aerolizer, Diskus, Turbuhaler, and Easyhaler using their "real-life" DPI inhalation technique. These are low-, medium-, medium/high-, and high-resistance DPIs, respectively. The inhalation flow against time was recorded to provide the peak inhalation flow (PIF; in L/min), the maximum pressure change (ΔP; in kPa), acceleration rates (ACCEL; in kPa/sec), time to maximum inhalation, the length of each inhalation (in sec), and the inhalation volume (IV; in liters) of each inhalation maneuver. PIF, ΔP, and ACCEL values were consistent with the order of the inhaler's resistance. For each device, the inhalation characteristics were in the order ADULT>COPD>CHILD for PIF, ΔP, and ACCEL (p<0.001). The results showed a large variability in inhalation characteristics and demonstrate the advantages of ΔP and ACCEL rather than PIFs. Overall inhaled volumes were low, and only one patient achieved an IV >4 L and ΔP >4 kPa. The large variability of these inhalation characteristics and their range highlights that if inhalation profiles were used with compendial in vitro dose emission measurements, then the results would provide useful information about the dose patients inhale during routine use. The inhalation characteristics highlight that adults with asthma have greater inspiratory capacity than patients with COPD, whereas children with asthma have the lowest. The significance of the inhaled volume to empty doses from each device requires investigation.

A Comparison of "Total Dust" and Inhalable Personal Sampling for Beryllium Exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carter, Colleen M.

2012-05-09

In 2009, the American Conference of Governmental Industrial Hygienists (ACGIH) reduced the Beryllium (Be) 8-hr Time Weighted Average Threshold Limit Value (TLV-TWA) from 2.0 μg/m 3 to 0.05 μg/m 3 with an inhalable 'I' designation in accordance with ACGIH's particle size-selective criterion for inhalable mass. Currently, per the Department of Energy (DOE) requirements, the Lawrence Livermore National Laboratory (LLNL) is following the Occupational Health and Safety Administration (OSHA) Permissible Exposure Limit (PEL) of 2.0 μg/m 3 as an 8-hr TWA, which is also the 2005 ACGIH TLV-TWA, and an Action Level (AL) of 0.2 μg/m 3 and sampling is performedmore » using the 37mm (total dust) sampling method. Since DOE is considering adopting the newer 2009 TLV guidelines, the goal of this study was to determine if the current method of sampling using the 37mm (total dust) sampler would produce results that are comparable to what would be measured using the IOM (inhalable) sampler specific to the application of high energy explosive work at LLNL's remote experimental test facility at Site 300. Side-by-side personal sampling using the two samplers was performed over an approximately two-week period during chamber re-entry and cleanup procedures following detonation of an explosive assembly containing Beryllium (Be). The average ratio of personal sampling results for the IOM (inhalable) vs. 37-mm (total dust) sampler was 1.1:1 with a P-value of 0.62, indicating that there was no statistically significant difference in the performance of the two samplers. Therefore, for the type of activity monitored during this study, the 37-mm sampling cassette would be considered a suitable alternative to the IOM sampler for collecting inhalable particulate matter, which is important given the many practical and economic advantages that it presents. However, similar comparison studies would be necessary for this conclusion to be applied to other types of activities, where earlier studies have shown that the IOM sampler tends to collect higher concentrations of Be compared to the 37-mm cassette, which could complicate compliance with what is already an extremely low exposure limit.« less

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation

PubMed Central

Mangal, Sharad; Nie, Haichen; Xu, Rongkun; Guo, Rui; Cavallaro, Alex; Zemlyanov, Dmitry; Zhou, Qi (Tony)

2018-01-01

Purpose Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. Methods The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. Results The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. Conclusions We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine. PMID:29374368

A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood

PubMed Central

Wintner, Edward A; Deckwerth, Thomas L; Langston, William; Bengtsson, Asa; Leviten, Dina; Hill, Paul; Insko, Michael A; Dumpit, Ronald; VandenEkart, Emily; Toombs, Christopher F; Szabo, Csaba

2010-01-01

Background and purpose: Hydrogen sulphide (H2S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H2S in blood and tissues. Experimental approach: Concentrations of reactive sulphide in saline and freshly drawn whole blood were quantified by reaction with the thio-specific derivatization agent monobromobimane, followed by reversed-phase fluorescence HPLC and/or mass spectrometry. In pharmacokinetic studies, male rats were exposed either to intravenous infusions of sodium sulphide or to H2S gas inhalation, and levels of available blood sulphide were measured. Levels of dissolved H2S/HS- were concomitantly measured using an amperometric sensor. Key results: Monobromobimane was found to rapidly and quantitatively derivatize sulphide in saline or whole blood to yield the stable small molecule sulphide dibimane. Extraction and quantification of this bis-bimane derivative were validated via reversed-phase HPLC separation coupled to fluorescence detection, and also by mass spectrometry. Baseline levels of sulphide in blood were in the range of 0.4–0.9 µM. Intravenous administration of sodium sulphide solution (2–20 mg·kg−1·h−1) or inhalation of H2S gas (50–400 ppm) elevated reactive sulphide in blood in a dose-dependent manner. Each 1 mg·kg−1·h−1 of sodium sulphide infusion into rats was found to be pharmacokinetically equivalent to approximately 30 ppm of H2S gas inhalation. Conclusions and implications: The monobromobimane derivatization method is a sensitive and reliable means to measure reactive sulphide species in whole blood. Using this method, we have established a bioequivalence between infused sodium sulphide and inhaled H2S gas. PMID:20590590

A monobromobimane-based assay to measure the pharmacokinetic profile of reactive sulphide species in blood.

PubMed

Wintner, Edward A; Deckwerth, Thomas L; Langston, William; Bengtsson, Asa; Leviten, Dina; Hill, Paul; Insko, Michael A; Dumpit, Ronald; VandenEkart, Emily; Toombs, Christopher F; Szabo, Csaba

2010-06-01

Hydrogen sulphide (H(2)S) is a labile, endogenous metabolite of cysteine, with multiple biological roles. The development of sulphide-based therapies for human diseases will benefit from a reliable method of quantifying H(2)S in blood and tissues. Concentrations of reactive sulphide in saline and freshly drawn whole blood were quantified by reaction with the thio-specific derivatization agent monobromobimane, followed by reversed-phase fluorescence HPLC and/or mass spectrometry. In pharmacokinetic studies, male rats were exposed either to intravenous infusions of sodium sulphide or to H(2)S gas inhalation, and levels of available blood sulphide were measured. Levels of dissolved H(2)S/HS(-) were concomitantly measured using an amperometric sensor. Monobromobimane was found to rapidly and quantitatively derivatize sulphide in saline or whole blood to yield the stable small molecule sulphide dibimane. Extraction and quantification of this bis-bimane derivative were validated via reversed-phase HPLC separation coupled to fluorescence detection, and also by mass spectrometry. Baseline levels of sulphide in blood were in the range of 0.4-0.9 microM. Intravenous administration of sodium sulphide solution (2-20 mg x kg(-1) x h(-1)) or inhalation of H(2)S gas (50-400 ppm) elevated reactive sulphide in blood in a dose-dependent manner. Each 1 mg x kg(-1) x h(-1) of sodium sulphide infusion into rats was found to be pharmacokinetically equivalent to approximately 30 ppm of H(2)S gas inhalation. The monobromobimane derivatization method is a sensitive and reliable means to measure reactive sulphide species in whole blood. Using this method, we have established a bioequivalence between infused sodium sulphide and inhaled H(2)S gas.

Physical characteristics and aerosolization performance of insulin dry powders for inhalation prepared by a spray drying method.

PubMed

You, Yu; Zhao, Min; Liu, Guangli; Tang, Xing

2007-07-01

The objective of this study was to investigate the influence of formulation excipients on the physical characteristics and aerosolization performance of insulin dry powders for inhalation. Insulin dry powders were prepared by a spray drying technique using excipients such as sugars (trehalose, lactose and dextran), mannitol and amino acids (L-leucine, glycine and threonine). High performance liquid chromatography and the mouse blood glucose method were used for determination of the insulin content. The powder properties were determined and compared by scanning electron microscopy, thermo-gravimetric analysis and size distribution analysis by a time-of-flight technique. The in-vitro aerosolization behaviour of the powders was assessed with an Aerolizer inhaler using a twin-stage impinger. Powder yield and moisture absorption were also determined. Results showed that there was no noticeable change in insulin content in any of the formulations by both assay methods. All powders were highly wrinkled, with median aerodynamic diameters of 2-4 microm, and consequently suitable for pulmonary administration. The tapped density was reduced dramatically when glycine was added. The powders containing mannitol, with or without L-leucine, were less sensitive to moisture. The highest respirable fraction of 67.3 +/- 1.3% was obtained with the formulation containing L-leucine, in contrast to formulations containing glycine and threonine, which had a respirable fraction of 11.2 +/- 3.9% and 23.5 +/- 2.5%, respectively. In addition, powders with good physical properties were achieved by the combination of insulin and trehalose. This study suggests that L-leucine could be used to enhance the aerosolization behaviour of the insulin dry powders for inhalation, and trehalose could potentially be used as an excipient in the formulations.

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation.

PubMed

Mangal, Sharad; Nie, Haichen; Xu, Rongkun; Guo, Rui; Cavallaro, Alex; Zemlyanov, Dmitry; Zhou, Qi Tony

2018-01-08

Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.

Optimized pulmonary gene transfection in mice by spray-freeze dried powder inhalation.

PubMed

Mohri, Kohta; Okuda, Tomoyuki; Mori, Asami; Danjo, Kazumi; Okamoto, Hirokazu

2010-06-01

Spray-freeze drying (SFD) is an attractive technique to prepare highly porous dry powders for inhalation. However, there have been few reports of its application to dry powder inhalers (DPIs). Therefore, in this study, we prepared dry plasmid DNA (pDNA) powders with different molecular ratios of chitosan to pDNA (N/P ratios) by SFD. All the pDNA powders were spherical and highly porous, with particles approximately 20-40microm in geometric diameter. The morphology changed little with the alteration of the N/P ratio. On electrophoresis, a band of linear pDNA was detected in the preparation without chitosan, suggesting the destabilization of pDNA through SFD. However, the addition of chitosan protected pDNA from destabilization. Moreover, the pDNA powders were evaluated for pulmonary gene transfection efficiency using an in vivo dual imaging technique for gene DPIs developed previously. Maximum gene expression was observed at 9-12h following pulmonary administration of the powders into mice. The powder with the N/P ratio of 10 had the highest gene transfection efficiency. A higher affinity of chitosan for pDNA and a smaller (approximately 100nm) pDNA/chitosan complex (N/Pf10) were found at pH 6.5 (in lung) than at pH 7.4 (in physiological conditions), suggesting that the effective compaction of pDNA by chitosan at the N/P ratio of 10 at pH 6.5 contributes to the gene transfection efficiency in the lung. These results suggest inhalable dry pDNA powders with chitosan prepared by SFD to be a suitable formulation for pulmonary gene therapy. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

PubMed Central

Pravetoni, M; Keyler, DE; Raleigh, MD; Harris, AC; LeSage, MG; Mattson, CK; Pettersson, S; Pentel, PR

2011-01-01

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 minute nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a two hour whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular midday smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 hr smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 hr WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation. PMID:21333633

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.

CFD simulation of aerosol delivery to a human lung via surface acoustic wave nebulization.

PubMed

Yousefi, Morteza; Pourmehran, Oveis; Gorji-Bandpy, Mofid; Inthavong, Kiao; Yeo, Leslie; Tu, Jiyuan

2017-12-01

Administration of drug in the form of particles through inhalation is generally preferable in the treatment of respiratory disorders. Conventional inhalation therapy devices such as inhalers and nebulizers, nevertheless, suffer from low delivery efficiencies, wherein only a small fraction of the inhaled drug reaches the lower respiratory tract. This is primarily because these devices are not able to produce a sufficiently fine drug mist that has aerodynamic diameters on the order of a few microns. This study employs computational fluid dynamics to investigate the transport and deposition of the drug particles produced by a new aerosolization technique driven by surface acoustic waves (SAWs) into an in silico lung model geometrically reconstructed using computed tomography scanning. The particles generated by the SAW are released in different locations in a spacer chamber attached to a lung model extending from the mouth to the 6th generation of the lung bronchial tree. An Eulerian approach is used to solve the Navier-Stokes equations that govern the airflow within the respiratory tract, and a Lagrangian approach is adopted to track the particles, which are assumed to be spherical and inert. Due to the complexity of the lung geometry, the airflow patterns vary as it penetrates deeper into the lung. High inertia particles tend to deposit at locations where the geometry experiences a significant reduction in cross section. Our findings, nevertheless, show that the injection location can influence the delivery efficiency: Injection points close to the spacer centerline result in deeper penetration into the lung. Additionally, we found that the ratio of drug particles entering the right lung is significantly higher than the left lung, independent of the injection location. This is in good agreement with this fact that the most of airflow enters to the right lobes.

Effectiveness of Nurse-Driven Inhaler Education on Inhaler Proficiency and Compliance Among Obstructive Lung Disease Patients: A Quasi-Experimental Study.

PubMed

Al-Kalaldeh, Mahmoud; El-Rahman, Mona Abd; El-Ata, Amal

2016-06-01

Background Health education on proper inhaler usage is the most feasible and accessible strategy to increase inhaler effectiveness. Purpose To assess the impact of nurse-driven inhaler education on the compliance and proficiency of using inhalers among inhaler users. Methods This single-center, quasi-experimental study included the implementation of an individualized 60-min educational session on inhalers use. Health education and pretest and posttest outcomes were assessed by the Inhaler Proficiency Schedule and Patient Reported Behaviour tools. Results One hundred and twenty-one participants joined the study. At pretest, participants showed inadequate knowledge of general inhaler use. No previous training had been received by participants and difficulty with use and complications from using the inhalers were reported. At posttest, participants reported improvement in inhaler proficiency scores from 5.72 to 8.60 ( t = 17.99, df = 220, p < 0.001). Likewise, they showed a significant reduction towards the noncompliant behaviors from 15.21 to 11.19 ( t = 16.388, df = 238, p < 0.001). Conclusions Nurse-driven inhaler education yielded positive outcomes in both inhaler proficiency and compliance. The patients' assessment of using inhalers is crucial to determine the patients' educational deficits.

Checklists for the Assessment of Correct Inhalation Therapy.

PubMed

Knipel, V; Schwarz, S; Magnet, F S; Storre, J H; Criée, C P; Windisch, W

2017-02-01

Introduction  For the long-term treatment of obstructive lung diseases inhalation therapy with drugs being delivered directly to the lungs as an aerosol has become the method of choice. However, patient-related mistakes in inhalation techniques are frequent and recognized to be associated with reduced disease control. Since the assessment of patient-mistakes in inhalation has yet not been standardized, the present study was aimed at developing checklists for the assessment of correct inhalation. Methods  Checklists were developed in German by an expert panel of pneumologists and professionally translated into English following back-translation procedures. The checklists comparably assessed three major steps of inhalation: 1) inhalation preparation, 2) inhalation routine, and 3) closure of inhalation. Results  Checklists for eight frequently used inhalers were developed: Aerolizer, Breezhaler, Diskus (Accuhaler), metered-dose inhaler, Handihaler, Novolizer, Respimat, Turbohaler. Each checklist consists of ten items: three for inhalation preparation, six for inhalation routine, and one for closure of inhalation. Discussion  Standardized checklists for frequently used inhalers are available in German and English. These checklists can be used for clinical routines or for clinical trials. All checklists can be downloaded free of charge for non-profit application from the homepage of the German Airway League (Deutsche Atemwegsliga e. V.): www.atemwegsliga.de. © Georg Thieme Verlag KG Stuttgart · New York.

[The development of vaporizers. A question of precise dose].

PubMed

Petermann, Heike

2009-05-01

Since the beginning of anaesthesia it was well known that anaesthetic agents administered by inhalation must be capable of existing in gaseous form. For vaporization various types tried to work accurately. Since oxygen was available there could be realized new concepts like the principles of injection or bubble through. With Copper Kettle (1948) for ether and chloroform and Draeger Vapor (1958) for Halothane accurate administration of volatile anaesthetics was available. Today vaporizers are part of anaesthetic machines.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

PubMed

Kogan, F M; Nikitina, O V

1994-10-01

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

PubMed Central

Kogan, F M; Nikitina, O V

1994-01-01

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity. PMID:7882932

Environmental enrichment reverses memory impairment induced by toluene in mice.

PubMed

Montes, Sergio; Solís-Guillén, Rocío Del Carmen; García-Jácome, David; Páez-Martínez, Nayeli

2017-05-01

Toluene is the main component of a variety of inhalants that are used for intoxication purposes. Alterations in memory have been reported in inhalant users; however, it is unclear whether these impairments could be reversed, and the mechanisms involved in the putative recovery. Therefore, the main purpose of this study was to model the deleterious effects of toluene on memory in mice and to evaluate the effect of environmental enrichment on that response. In the second part of the study, the concentrations of glutamate and GABA, following chronic toluene exposure and after environmental enrichment treatment, were evaluated. Adolescent mice were exposed to either a single or repeated schedule of toluene administration and their responses to object recognition were analyzed. An independent group of mice was repeatedly exposed to toluene and then housed either under environmental enrichment or standard conditions for four weeks. At the end of the housing period, the rodents' performance in object recognition test, as well as the concentrations of neurotransmitters, were analyzed. The results showed that toluene caused memory impairment in mice that received a single or repeated solvent exposure. Remarkably, environmental enrichment could reverse memory deficits induced by repeated administration of toluene. Cessation of toluene exposure in mice in standard housing did not produce that response. The glutamate and GABA tissue contents were not involved in the effects of toluene or environmental enrichment of memory. Copyright © 2017. Published by Elsevier Inc.

Non-Clinical Safety Evaluation of Intranasal Iota-Carrageenan

PubMed Central

Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

2015-01-01

Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug’s action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application. PMID:25875737

Non-clinical safety evaluation of intranasal iota-carrageenan.

PubMed

Hebar, Alexandra; Koller, Christiane; Seifert, Jan-Marcus; Chabicovsky, Monika; Bodenteich, Angelika; Bernkop-Schnürch, Andreas; Grassauer, Andreas; Prieschl-Grassauer, Eva

2015-01-01

Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded) iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

In vitro synthesis and characterisation of three fenoterol sulfoconjugates detected in fenoterol post-administration urine samples.

PubMed

Orlovius, A K; Guddat, S; Gütschow, M; Thevis, M; Schänzer, W

2013-11-01

Fenoterol, a fast-acting β2-adrenergic agonist, is used in the therapy of obstructive pulmonary diseases and for the inhibition of premature labour obstetrics. Doping control for β2-agonists, which are prohibited in sports by the World Anti-Doping Agency, is commonly performed by liquid chromatography/mass spectrometry after hydrolysis of phase II metabolites. The continuing development of analytical procedures has led to direct injection of urine samples without sample preparation becoming a viable tool. For the detection of substances without sample preparation, including hydrolysis, detailed information of the phase II metabolism of the substances is essential. In this study, human S9 fractions of different tissues and two recombinant sulfotransferases were investigated for their potential to form fenoterol sulfoconjugates, which were characterised in detail. Two mono-sulfoconjugates and one bis-sulfoconjugate were synthesised and their structures confirmed by liquid chromatography–high-resolution/high-accuracy mass spectrometry. All of the metabolites were identified as esterified phenolic compounds. Excretion studies with orally and inhalatively administered fenoterol proved the occurrence of the sulfoconjugates in vivo. Inhalatively administered fenoterol resulted in the detection of the two monosulfoconjugates in low amounts in urine due to the lower inhalation dose of fenoterol compared to the oral dose. After oral uptake of fenoterol, the two mono-sulfoconjugates and a fenoterol bis-sulfoconjugate were detected in urine. This is the first report of the bis-sulfoconjugate.

The US and EU regulatory landscapes for locally acting generic/hybrid inhalation products intended for treatment of asthma and COPD.

PubMed

Fuglsang, Anders

2012-08-01

This is a review of the current regulatory requirements associated with development and submission of abridged dossiers for locally acting inhalation drugs intended for the treatment of asthma and chronic obstructive pulmonary disease. The current EU law does not provide for submission of such products as generics due to the definition of bioequivalence and bioavailability; instead they must be submitted as hybrids. A guideline from 2009 is available that suggests a stepwise approach toward approval. An applicant should first consider the degree of in vitro match with the reference product; provided that the match is extensive, approval may be granted. If the in vitro match cannot be proven, the next step is comparison of lung deposition and systemic exposure. If this match is proven, approval may be granted; otherwise, the final step is pharmacodynamic evaluation. In the United States, submission as a generic is possible, but only a single specific guidance document from 1989 is in force. It describes in vitro requirements for comparison of albuterol and metaproterenol pressurized metered dose inhalers. Applicants are encouraged to seek dialogue with regulators prior to and during development. Although parallel scientific advice procedures have been established between the US Food and Drug Administration and the European Medicines Agency, the two authorities give independent and individual advice.

The effects of mannitol on the transport of ciprofloxacin across respiratory epithelia.

PubMed

Ong, Hui Xin; Traini, Daniela; Salama, Rania; Anderson, Sandra D; Daviskas, Evangelia; Young, Paul M

2013-08-05

Inhalation of antibiotics and mucolytics is the most important combination of inhaled drugs for chronic obstructive lung diseases and has become a standard part of treatment. However, it is yet to be determined whether the administration of a mucolytic has an effect on the transport rate of antibiotics across the airway epithelial cells. Consequently, the aim of this study was to investigate the effects of inhalation dry powder, specifically mannitol, on ciprofloxacin transport using a Calu-3 air-interface cell model. Transport studies of ciprofloxacin HCl were performed using different configurations including single spray-dried ciprofloxacin alone, co-spray-dried ciprofloxacin with mannitol, and deposition of mannitol prior to ciprofloxacin deposition. To understand the mechanism of transport and interactions between the drugs, pH measurements of apical surface liquid (ASL) and further transport studies were performed with ciprofloxacin base, with and without the presence of ion channel/transport inhibitors such as disodium cromoglycate and furosemide. Mannitol was found to delay absorption of ciprofloxacin HCl through the increase in ASL volume and subsequent reduction in pH. Conversely, ciprofloxacin base had a higher transport rate after mannitol deposition. This study clearly demonstrates that the deposition of mannitol prior to ciprofloxacin on the air-interface Calu-3 cell model has an effect on its transport rate. This was also dependent on the salt form of the drug and the timing and sequence of formulations administered.

Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. The Paris-Sud University Lung Transplantation Group.

PubMed

Murakami, S; Bacha, E A; Mazmanian, G M; Détruit, H; Chapelier, A; Dartevelle, P; Hervé, P

1997-08-01

Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.

Sarcoendoplasmic reticulum Ca(2+) ATPase. A critical target in chlorine inhalation-induced cardiotoxicity.

PubMed

Ahmad, Shama; Ahmad, Aftab; Hendry-Hofer, Tara B; Loader, Joan E; Claycomb, William C; Mozziconacci, Olivier; Schöneich, Christian; Reisdorph, Nichole; Powell, Roger L; Chandler, Joshua D; Day, Brian J; Veress, Livia A; White, Carl W

2015-04-01

Autopsy specimens from human victims or experimental animals that die due to acute chlorine gas exposure present features of cardiovascular pathology. We demonstrate acute chlorine inhalation-induced reduction in heart rate and oxygen saturation in rats. Chlorine inhalation elevated chlorine reactants, such as chlorotyrosine and chloramine, in blood plasma. Using heart tissue and primary cardiomyocytes, we demonstrated that acute high-concentration chlorine exposure in vivo (500 ppm for 30 min) caused decreased total ATP content and loss of sarcoendoplasmic reticulum calcium ATPase (SERCA) activity. Loss of SERCA activity was attributed to chlorination of tyrosine residues and oxidation of an important cysteine residue, cysteine-674, in SERCA, as demonstrated by immunoblots and mass spectrometry. Using cardiomyocytes, we found that chlorine-induced cell death and damage to SERCA could be decreased by thiocyanate, an important biological antioxidant, and by genetic SERCA2 overexpression. We also investigated a U.S. Food and Drug Administration-approved drug, ranolazine, used in treatment of cardiac diseases, and previously shown to stabilize SERCA in animal models of ischemia-reperfusion. Pretreatment with ranolazine or istaroxime, another SERCA activator, prevented chlorine-induced cardiomyocyte death. Further investigation of responsible mechanisms showed that ranolazine- and istaroxime-treated cells preserved mitochondrial membrane potential and ATP after chlorine exposure. Thus, these studies demonstrate a novel critical target for chlorine in the heart and identify potentially useful therapies to mitigate toxicity of acute chlorine exposure.

Repeated allergen exposure enhances excitatory nonadrenergic noncholinergic nerve-mediated bronchoconstriction in sensitized guinea-pigs.

PubMed

Kageyama, N; Ichinose, M; Igarashi, A; Miura, M; Yamauchi, H; Sasaki, Y; Ishikawa, J; Tomaki, M; Shirato, K

1996-07-01

The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.

Practical aspects of inhaler use in the management of chronic obstructive pulmonary disease in the primary care setting.

PubMed

Yawn, Barbara P; Colice, Gene L; Hodder, Rick

2012-01-01

Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity. Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians. The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids. There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting. Patients' comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use. This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques. Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD.

Practical aspects of inhaler use in the management of chronic obstructive pulmonary disease in the primary care setting

PubMed Central

Yawn, Barbara P; Colice, Gene L; Hodder, Rick

2012-01-01

Sustained bronchodilation using inhaled medications in moderate to severe chronic obstructive pulmonary disease (COPD) grades 2 and 3 (Global Initiative for Chronic Obstructive Lung Disease guidelines) has been shown to have clinical benefits on long-term symptom control and quality of life, with possible additional benefits on disease progression and longevity. Aggressive diagnosis and treatment of symptomatic COPD is an integral and pivotal part of COPD management, which usually begins with primary care physicians. The current standard of care involves the use of one or more inhaled bronchodilators, and depending on COPD severity and phenotype, inhaled corticosteroids. There is a wide range of inhaler devices available for delivery of inhaled medications, but suboptimal inhaler use is a common problem that can limit the clinical effectiveness of inhaled therapies in the real-world setting. Patients’ comorbidities, other physical or mental limitations, and the level of inhaler technique instruction may limit proper inhaler use. This paper presents information that can overcome barriers to proper inhaler use, including issues in device selection, steps in correct technique for various inhaler devices, and suggestions for assessing and monitoring inhaler techniques. Ensuring proper inhaler technique can maximize drug effectiveness and aid clinical management at all grades of COPD. PMID:22888221

Teaching inhaler use in chronic obstructive pulmonary disease patients.

PubMed

Lareau, Suzanne C; Hodder, Richard

2012-02-01

To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. Review of the national and international scientific literature. Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

Inhaled Asthma Medications

MedlinePlus

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

Budesonide nanocrystal-loaded hyaluronic acid microparticles for inhalation: In vitro and in vivo evaluation.

PubMed

Liu, Tingting; Han, Meihua; Tian, Fang; Cun, Dongmei; Rantanen, Jukka; Yang, Mingshi

2018-02-01

Most inhaled pharmaceutical formulations on the market are intended to exert immediate pharmacological action, even although inhaled sustained-release formulations can be needed to reduce the frequency of dosing. The purpose of this study was to investigate the pulmonary retention and pharmacokinetics of a poorly water-soluble drug after loading its nanocrystal form into inhalable mucoadhesive microparticles composed of hyaluronic acid. It was intended to prolong the pharmacological effect without compromising the dissolution rate of the poorly water-soluble drug. In this study, budesonide, a corticosteroid anti-inflammatory drug, was used as a model poorly water-soluble drug. Submicron budesonide particles were prepared by wet ball milling, and subsequently loaded into hyaluronic acid microparticles by the spray drying process. The ball-milled budesonide particles and the spray-dried microparticles were characterized using dynamic light scattering (DLS), laser diffraction, Scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). Selected formulations were evaluated in terms of their dissolution/release rate, aerosol performance, muco-adhesion and pharmacokinetics in rats. As shown by XRD and DSC analysis, the nanonized budesonide particles in this study were mainly in crystalline form. The dissolution/release study showed that the in vitro release of budesonide from the microparticles was not significantly sustained compared with the dissolution rate of budesonide nanocrystals (BUD-NC). However, the budesonide in the microparticles exhibited prolonged retention on the surface of porcine tracheal tube owing to the muco-adhesion ability of hyaluronic acid. After intratracheal administration to rats, the BUD-NC exhibited a similar pharmacokinetic profile to that of budesonide solution via i.v. injection. In contrast, budesonide loaded in the mucoadhesive microparticles exhibited a significantly prolonged T max and increased bioavailability with the animal model. This study demonstrated that inhaled microparticles composed of hyaluronic acid could produce sustained budesonide pharmacological effects. This can be attributed to the mucoadhesion of the polymer that overcame the mucociliary clearance and, consequently, prolonged the retention of the active substance in the lung without necessarily reducing the in vitro dissolution rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man

NASA Astrophysics Data System (ADS)

Hori, Yuki; Hirano, Yoshiyuki; Koshino, Kazuhiro; Moriguchi, Tetsuaki; Iguchi, Satoshi; Yamamoto, Akihide; Enmi, Junichiro; Kawashima, Hidekazu; Zeniya, Tsutomu; Morita, Naomi; Nakagawara, Jyoji; Casey, Michael E.; Iida, Hidehiro

2014-09-01

Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the feasibility of using a state-of-the-art 3D PET scanner in the quantitative PET imaging during inhalation of 15O labeled oxygen.

Derivation of a human equivalent concentration for n-butanol using a physiologically based pharmacokinetic model for n-butyl acetate and metabolites n-butanol and n-butyric acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teeguarden, Justin G.; Deisinger, P. J.; Poet, Torka S.

2005-05-01

The metabolic series (family) approach for risk assessment uses a dosimetry-based analysis to develop toxicity information for a group of metabolically linked compounds using pharmacokinetic (PK) data for each compound and toxicity data for the parent compound. An initial physiologically-based pharmacokinetic (PBPK) model was developed to support the implementation of the metabolic series approach for n-butyl acetate and its subsequent metabolites, n-butanol, and n-butyric acid (the butyl series) (Barton et al. 2000). In conjunction with pilot pharmacokinetic studies, the model was used to design the definitive intravenous (i.v.) PK studies. Rats were implanted with dual indwelling cannulae and administered testmore » compounds by i.v. bolus dose, i.v. infusion, or by inhalation in a recirculating closed chamber. Hepatic, vascular and extravascular metabolic constants for metabolism were estimated by fitting the model to the blood time course data from these experiments. The respiratory bioavailability of n-butyl acetate and n-butanol was estimated from closed chamber inhalation studies and measured ventilation rates. The resulting butyl series PBPK model successfully reproduces the blood time course of these compounds following i.v. administration, and inhalation exposure to n-butyl acetate and n-butanol. A fully scaled human version of the model successfully reproduces arterial blood n-butanol kinetics following inhalation exposure to n-butanol. These validated i.v (rat) and inhalation route models (rat, butyl acetate, n-butanol; human, butanol only) can be used to support species and dose-route extrapolations required for risk assessment of butyl series family of compounds. Further, this work demonstrates the usefulness of i.v. kinetic data for parameterization of systemic metabolism and the value of collaboration between experimentalists and kineticists in the development of PBPK models. The product of this effort, validated rat and human PBPK models for the butyl series compounds, illustrates the effectiveness of broad multi-institutional public/private collaborations in the pursuit of developing state of the art tools for risk assessment.« less

Financial effect of converting ipratropium-albuterol therapy from inhalers to nebulizer treatments at an academic health system.

PubMed

Loborec, Steven M; Johnson, Shawn E; Keating, Ellen A

2016-02-01

The results of a study to assess the financial impact of an automatic formulary substitution of ipratropium-albuterol nebulization solution for ipratropium-albuterol metered-dose inhalers (MDIs) at an academic health system are reported. The study was conducted at a 1242-bed urban academic health system. Data were collected regarding all respiratory medication administrations during a three-month period before the MDI-to-nebulizer substitution (October-December 2012) and the same period of 2013 (after the substitution was implemented). Purchasing data were compared between the two time periods to measure the impact of the formulary substitution on pharmacy department costs, and documented administrations were assessed to evaluate associated changes in respiratory therapist (RT) workload. With 100% prescriber compliance with the formulary substitution, the number of MDI administrations of ipratropium-albuterol declined from 13,667 in October-December 2012 to zero in the same period of 2013. The substitution required expenditures for equipment (vibrating mesh nebulizer technology and patient-specific kits) and RT personnel (one additional RT was hired), but those added costs were substantially outweighed by cost savings resulting from a substantial reduction in overall respiratory drug spending. An automatic substitution of ipratropium-albuterol nebulization solution for MDIs resulted in a three-month savings of $99,359 in drug cost and an extrapolated full-year savings of $397,436. When additional costs associated with the substitution were taken into account, there was an overall savings of $146,806 during the implementation year and a projected savings of $257,936 for each following year. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Qualitative and Quantitative Characteristics of the Electroencephalogram in Normal Horses during Administration of Inhaled Anesthesia.

PubMed

Williams, D C; Brosnan, R J; Fletcher, D J; Aleman, M; Holliday, T A; Tharp, B; Kass, P H; LeCouteur, R A; Steffey, E P

2016-01-01

The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. Six healthy horses. Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded. Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only. Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Short-term increase of serum troponin I and serum heart-type fatty acid-binding protein (H-FABP) in dogs following administration of formoterol.

PubMed

Strauss, Volker; Wöhrmann, Thomas; Frank, Ilona; Hübel, Ulrich; Luft, Jörg; Bode, Gerd; Germann, Paul-Georg

2010-07-01

In this paper, changes in serum levels of the cardiac biomarkers troponin I and the heart-type fatty acid-binding protein (H-FABP) following administration of a long-acting beta(2)-sympathicomimeticum (long-acting beta-agonist, LABA) to dogs were measured. We measured troponin I in dogs in a 4-week repeated-dose study with inhalative administration of formoterol (13microg/kgd) and a glucocorticoid/formoterol combination (143/16microg/kgd). The medians of troponin I increased within 3 days in both groups, far beyond the cut-off level (0.1microg/L), but returned to baseline levels on study day 9. The increase was more pronounced in the formoterol-only group (3.29microg/L) compared to the glucocorticoid/formoterol combination group (1.32microg/L). In a second study, we measured serum troponin I as well as serum H-FABP levels in several samples over 7 days in dogs, receiving a single inhalative dose of a glucocorticoid/formoterol combination (120/12mug/kgd). The median of the troponin I concentration increased above the cut-off level within 2h and that of H-FABP within 4h. The medians of both parameters were temporarily above the cut-off levels even on study day 7. Both studies were conducted according to national animal welfare guidelines. To our knowledge, this is the first report that shows a corresponding increase of troponin I and H-FABP in dogs treated with formoterol. Both parameters are more sensitive in detecting a drug-induced cardiac injury compared to total LDH, total CK as well as CK MB activity. However, it is recommended to take at least three blood samples per day to assess a temporary increase of troponin I.

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

PubMed Central

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

2015-01-01

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

Benzene metabolite levels in blood and bone marrow of B6C3F{sub 1} mice after low-level exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bechtold, W.E.; Strunk, M.R.; Thornton-Manning, J.R.

1995-12-01

Studies at the Inhalation Toxicology Research Institute (ITRI) have explored the species-specific uptake and metabolism of benzene. Results have shown that metabolism is dependent on both dose and route of administration. Of particular interest were shifts in the major metabolic pathways as a function of exposure concentration. In these studies, B6C3F{sub 1} mice were exposed to increasing levels of benzene by either gavage or inhalation. As benzene internal dose increased, the relative amounts of muconic acid and hydroquinone decreased. In contrast, the relative amount of catechol increased with increasing exposure. These results show that the relative levels of toxic metabolitesmore » are a function of exposure level. Based on these results and assuming a linear relationship between exposure concentration and levels of bone marrow metabolites, it would be difficult to detect an elevation of any phenolic metabolites above background after occupational exposures to the OSHA Permissible Exposure Limit of 1 ppm benzene.« less

[Antiplatelet properties of nitrogen monoxide].

PubMed

Adrie, C

1996-11-01

Nitric (correction of nitrous) oxide (NO) plays a fundamental part in the haemostatic equilibrium between the endothelium and platelets, an equilibrium of established clinical importance in cardiovascular disease. NO stimulates the enzyme guanylate cyclase which is responsible for synthesis of GMPc, the increase of which results in platelet inhibition. Synthesis of NO may have endogenous auto or paracrine origine from platelets or endothelial cells and participates in the local regulation of platelet function in association with other products of endothelial or platelet synthesis. Exogenous administration is common in therapeutics either in molecules which release NO (nitrate derivatives, sodium nitropruside, molsidomine, etc) or by NO gas administered by inhalation. The antiplatelet effect of NO has been clearly demonstrated in vitro, in vivo or ex vivo, in animals and humans, and probably explains, at least partially, the efficacy of nitrate derivatives in ischaemic coronary artery disease. Nevertheless, the platelet inhibition observed with intravenous NO releasing drugs is associated with potentially harmful systemic hypotension. Platelet inhibition by inhalation of NO could be an alternative means of avoiding this unwanted effect.

Treatment options for the management of exercise-induced asthma and bronchoconstriction.

PubMed

Millward, David T; Tanner, Lindsay G; Brown, Mark A

2010-12-01

Treatment for exercise-induced bronchospasm and exercise-induced asthma includes both pharmacologic and nonpharmacologic options. Pharmacologic agents that have been proven to be effective for treating these conditions include short- and long-acting β2-adrenoceptor agonists, mast cell-stabilizing agents, anticholinergics, leukotriene receptor antagonists, and inhaled corticosteroids (ICS). When selecting the most appropriate medication, factors to consider include the effectiveness of each, the duration of action, frequency of administration, potential side effects, and tolerance level. Long-acting β2-adrenoceptor agonists should not be used without ICS. Nonpharmacologic treatments include physical conditioning, incorporating a warm-up before and a cool-down period after exercise, performing nasal breathing, avoiding cold weather or environmental allergens, using a face mask or other aid to warm and humidify inhaled air, and modifying dietary intake. The data to support nonpharmacologic treatments are limited; however, they are routinely recommended because of the low risk associated with their use. This article highlights the advantages and limitations of each treatment option.

A point-source outbreak of Coccidioidomycosis among a highway construction crew.

PubMed

Nicas, Mark

2018-01-01

Coccidioidomycosis is an infection caused by inhaling spores of the soil fungus Coccidioides immitis (hereafter termed Cocci). Cocci is endemic in certain areas of California. When soil containing the fungus is disturbed, as during earth-moving activities, respirable Cocci spores can become airborne and be inhaled by persons in the vicinity. This article describes a cluster of seven Cocciodioidomycosis cases among a highway construction crew that occurred in June/July 2008 in Kern County, CA, which is among the most highly endemic regions for Cocci in California. The exposures spanned no more than seven work days, and illness developed within two to three weeks of the exposures. Given the common source of exposure (soil dust generated at the work site) and the multiple cases occurring close in time, the cluster can also be termed a "point-source outbreak." The contractor was not informed of the infection risk and did not take adequate precautions against dust exposure. Appropriate engineering/administrative controls and respiratory protection are discussed.

[Clinical evaluation of Olbas oil effect on nasal mucosa in acute rhinitis patients during common cold].

PubMed

Zalewski, P; Olszewski, J; Olszewska-Ziaber, A; Zielińska-Bliźniewska, H; Pietkiewicz, P

1997-01-01

The aim of the study was the clinical evaluation of the effect of Olbas oil on nasal mucosa in patients with acute rhinitis during common cold. 15 patients with 2-3 days history of acute rhinitis during common cold, both sexes, in the age between 23-47 were investigated. All the examinations were done before using, after the first inhalation, and after 7 days of Olbas oil administration. The investigation before using Olbas oil was comprised of: history data, general and otorhinolaryngological examination with particular evaluation of nasal mucosa, anterior rhinomanometry, saccharin translocation time, olfactometry, microbiological cultures, histamine nasal provocation test. At the end, after 7 days of Olbas oil inhalation 3 times a day for 4 minutes 4 drops of Olbas oil applied into a handkerchief, all the test were done again, as at the beginning. The study showed a good of the effect of Olbas oil on nasal mucosa in patients with acute rhinitis during common cold.

Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja

The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mousemore » lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No accumulation of hgd40 was observed after multiple treatments. • Pharmacokinetic properties of hgd40 support convenient dose administration regimen.« less

Inhalant Use and Inhalant Use Disorders in the United States

PubMed Central

Howard, Matthew O.; Bowen, Scott E.; Garland, Eric L.; Perron, Brian E.; Vaughn, Michael G.

2011-01-01

More than 22 million Americans age 12 and older have used inhalants, and every year more than 750,000 use inhalants for the first time. Despite the substantial prevalence and serious toxicities of inhalant use, it has been termed “the forgotten epidemic.” Inhalant abuse remains the least-studied form of substance abuse, although research on its epidemiology, neurobiology, treatment, and prevention has accelerated in recent years. This review examines current findings in these areas, identifies gaps in the research and clinical literatures pertaining to inhalant use, and discusses future directions for inhalant-related research and practice efforts. PMID:22003419

[Did the patients with chronic obstructive pulmonary disease in Primary Care center Anton de Borja correctly utilize inhalers?].

PubMed

Represas-Carrera, Francisco Jesús

2015-01-01

To determine the percentage of patients with Pulmonary Obstructive Chronic Disease who doing of incorrect form the inhaler technique. Descriptive transversal study made in the Primary Care Center "Antón de Borja" of Rubi (in Barcelona) during the period between May and December 2013, where it was studied a representative sample of 200 patients. To assess the inhaler technique was performed a personal interview with the patient in which it was requested him to carry out a demonstration of how he was using his inhaler regularly evaluating his inhaler technique by means of the regulations established by Spanish Society of Pneumology and Thoracic Surgery. 43% of the patients carry out inhaler technique incorrectly. The percentage of inadequate use of inhalers of dry powder was 26%, of the pressurized cartridge 38% and the inhaler chamber 10%. 82% of patients ≥ 65 years who have prescribed a pressurized inhaler cartridge do not perform accompanied by an inhaler chamber. A high percentage of patients do not correctly carry out inhaler technique, pointing the rare use made of the inhaler chamber despite its proven efficacy and the high number of patients with pressurized inhaler cartridge. These results reflect the need for the implementation of an educational program in our Primary Care Center to teach patients to use inhaler devices. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Combined corticosteroid and long-acting beta-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease

PubMed Central

Nannini, Luis Javier; Cates, Christopher J; Lasserson, Toby J; Poole, Phillippa

2014-01-01

Background Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler may facilitate adherence to medication regimens, and improve efficacy. Objectives To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to placebo, in the treatment of adults with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. Selection criteria Studies were included if they were randomised and double-blind. Studies could compare any combined inhaled corticosteroids and long-acting beta-agonist preparation with placebo. Data collection and analysis Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia. Health-related quality of life (measured by validated scales), lung function and side-effects were secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios or rate ratios with 95% confidence intervals, and continuous data as mean differences and 95% confidence intervals. Main results Eleven studies met the inclusion criteria (6427 participants randomised). Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were used. Study quality was good. Fluticasone/salmeterol and budesonide/formoterol both reduced the rate of exacerbations. Pooled analysis of both combination therapies indicated that exacerbations were less frequent when compared with placebo, Rate Ratio: 0.74 (95% CI 0.7 to 0.8). The clinical impact of this effect depends on the frequency of exacerbations experienced by patients. The patients included in these trials had on average 1-2 exacerbations per year which means that treatment with combination therapy would lead to a reduction of one exacerbation every two to four years in these individuals. There is an overall reduction in mortality, but this outcome is dominated by the results of TORCH and further studies on budesonide/formoterol are required. The three year number needed to treat to prevent one extra death is 36 (95% CI 21 to 258), using a baseline risk of 15.2% from the placebo arm of TORCH. Both treatments led to statistically significant improvement in health status measurements, although the clinical importance of the differences observed is open to interpretation. Symptoms and lung function assessments favoured combination treatments. There was an increase in the risk of pneumonia with combined inhalers. The three year number needed to treat for one extra case of pneumonia is 13, using a baseline risk of 12.3% from the placebo arm of TORCH. Fewer participants withdrew from studies assessing combined inhalers due to adverse events and lack of efficacy. Authors’ conclusions Compared with placebo, combination therapy led to a significant reduction of a quarter in exacerbation rates. There was a significant reduction in all-cause mortality with the addition of data from the TORCH trial. The increased risk of pneumonia is a concern, and better reporting of this outcome in future studies would be helpful. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, particularly in relation to the profile of adverse events and benefits in relation to different doses of inhaled corticosteroids. PMID:17943798

Assessing fullness of asthma patients' aerosol inhalers.

PubMed

Rickenbach, M A; Julious, S A

1994-07-01

The importance of regular medication in order to control asthma symptoms is recognized. However, there is no accurate mechanism for assessing the fullness of aerosol inhalers. The contribution to asthma morbidity of unexpectedly running out of inhaled medication is unknown. A study was undertaken to determine how patients assess inhaler fullness and the accuracy of their assessments, and to evaluate the floatation method of assessing inhaler fullness. An interview survey of 98 patients (51% of those invited to take part), using 289 inhalers, was completed at one general practice in Hampshire. One third of participants said they had difficulty assessing aerosol inhaler fullness and those aged 60 years and over were found to be more inaccurate in assessing fullness than younger participants. Shaking the inhaler to feel the contents move was the commonest method of assessment. When placed in water, an inhaler canister floating on its side with a corner of the canister valve exposed to air indicates that the canister is less than 15% full (sensitivity 90%, specificity 99%). Floating a canister in water provides an objective measurement of aerosol inhaler fullness. Providing the method is recommended by the aerosol inhaler manufacturer, general practitioners should demonstrate the floatation method to patients experiencing difficulty in assessing inhaler fullness.

The impact of space travel on dosage form design and use.

PubMed

Aronsohn, A; Brazeau, G; Hughes, J

1999-07-01

The author speculates on potential factors that may influence the utilization of dosage forms in space. A key assumption is that most of the arguments will be based on current understanding of how dosage forms work on earth. Factors discussed include dosage form stability; and administration of drugs, particularly inhalation and aerosols. A sample experiment used a tissue culture model of drug transfer for passively absorbed drugs to address how alterations in hydrostatic pressure would change paracellular transport.

Microaerosol Administration of Synthetic β-γ-Dipalmitoyl-L-α-Lecithin in the Respiratory Distress Syndrome: A Preliminary Report

PubMed Central

Robillard, E.; Alarie, Y.; Dagenais-Perusse, P.; Baril, E.; Guilbeault, A.

1964-01-01

Synthetic L-α-lecithin was administered by inhalation to 11 infants suffering from respiratory distress. The L-α-lecithin was delivered by microaerosolization, at a concentration of 0.25% in a mixture of equal volumes of propylene glycol and water. This was done with the aim of decreasing the alveolar surface tension. In eight of the treated infants who survived, the respiratory distress was alleviated. The results are inconclusive but they justify further investigation. PMID:14104151

Cannabis Smoking and Cardiovascular Health: It's Complicated.

PubMed

Piano, M R

2017-08-01

Many states have legalized cannabis use for treatment of certain medical conditions or have legalized cannabis for recreational use. Consequently, cannabis use prevalence has escalated, giving rise to concerns about potential health effects. Cannabis smoking remains the most prevalent route of administration and is associated with inhalation of chemical toxicants. The aim of this article is to summarize the effects of cannabis smoking on the vasculature and occurrence of cardiovascular (CV) events such as myocardial infarction (MI) and stroke. © 2017 American Society for Clinical Pharmacology and Therapeutics.

An Unusual Case of Suicide Attempt Using Intravenous Injection of Kerosene.

PubMed

Hasan, M N; Sutradhar, S R; Ahmed, S M; Chowdhury, I H

2016-07-01

Kerosene belongs to the hydrocarbon group of compounds, used as a fuel for lamps, as well as heating and cooking in developing countries. Accidental kerosene poisoning and intoxication usually occur by inhalation or by occupational percutaneous absorption. Adults usually ingest kerosene for the purpose of self-harm, and children may ingest accidentally. Suicidal attempt using intravenous kerosene is an extra ordinary and very rare occurrence. A very few data are available regarding effects of intravenous administration of kerosene and its management.

The chemo and the mona: inhalants, devotion and street youth in Mexico City.

PubMed

Gigengack, Roy

2014-01-01

This paper understands inhalant use--the deliberate inhalation of volatile solvents or glues with intentions of intoxication--as a socially and culturally constituted practice. It describes the inhalant use of young street people in Mexico City from their perspective ("the vicioso or inhalant fiend's point of view"). Even if inhalant use is globally associated with economic inequality and deprivation, there is a marked lack of ethnography. Incomprehension and indignation have blocked our understanding of inhalant use as a form of marginalised drug use. The current explanation models reduce inhalant consumption to universal factors and individual motives; separating the practice from its context, these models tend to overlook gustatory meanings and experiences. The paper is informed by long-term, on-going fieldwork with young street people in Mexico City. Fieldwork was done from 1990 through 2010, in regular periods of fieldwork and shorter visits, often with Mexican colleagues. We created extensive sets of fieldnotes, which were read and re-read. "Normalcy" is a striking feature of inhalant use in Mexico City. Street-wise inhabitants of popular neighbourhoods have knowledge about inhalants and inhalant users, and act accordingly. Subsequently, Mexico City's elaborate street culture of sniffing is discussed, that is, the range of inhalants used, how users classify the substances, and their techniques for sniffing. The paper also distinguishes three patterns of inhalant use, which more or less correlate with age. These patterns indicate embodiments of street culture: the formation within users of gusto, that is, an acquired appetite for inhalants, and of vicio, the inhalant fiends' devotion to inhalants. What emerges from the ethnographic findings is an elaborate street culture of sniffing, a complex configuration of shared perspectives and embodied practices, which are shaped by and shaping social exclusion. These findings are relevant to appreciate and address the inhalant fiends' acquired appetite and habit. Copyright © 2013 Elsevier B.V. All rights reserved.

Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.

PubMed Central

Kirby, S. M.; Smith, J.; Ventresca, G. P.

1995-01-01

BACKGROUND--Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a. METHODS--The safety, tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in 12 healthy volunteers in a double blind, randomised crossover study using a cumulative dosing design. RESULTS--Safety and tolerability were similar and the response was related to the dose over the range used (50-400 micrograms) with both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences from the current inhaler for pulse rate, blood pressure, tremor, QTc interval, and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less effect on plasma potassium levels. CONCLUSIONS--In healthy volunteers the salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current salmeterol inhaler, and has similar systemic pharmacodynamic activity. PMID:7638815

Inhalation Therapy in Horses.

PubMed

Cha, Mandy L; Costa, Lais R R

2017-04-01

This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

Practice makes perfect: self-reported adherence a positive marker of inhaler technique maintenance.

PubMed

Azzi, Elizabeth; Srour, Pamela; Armour, Carol; Rand, Cynthia; Bosnic-Anticevich, Sinthia

2017-04-24

Poor inhaler technique and non-adherence to treatment are major problems in the management of asthma. Patients can be taught how to achieve good inhaler technique, however maintenance remains problematic, with 50% of patients unable to demonstrate correct technique. The aim of this study was to determine the clinical, patient-related and/or device-related factors that predict inhaler technique maintenance. Data from a quality-controlled longitudinal community care dataset was utilized. 238 patients using preventer medications where included. Data consisted of patient demographics, clinical data, medication-related factors and patient-reported outcomes. Mixed effects logistic regression was used to identify predictors of inhaler technique maintenance at 1 month. The variables found to be independently associated with inhaler technique maintenance using logistic regression (Χ 2 (3,n = 238) = 33.24, p < 0.000) were inhaler technique at Visit 1 (OR 7.1), device type (metered dose inhaler and dry powder inhalers) (OR 2.2) and self-reported adherent behavior in the prior 7 days (OR 1.3). This research is the first to unequivocally establish a predictive relationship between inhaler technique maintenance and actual patient adherence, reinforcing the notion that inhaler technique maintenance is more than just a physical skill. Inhaler technique maintenance has an underlying behavioral component, which future studies need to investigate. BEHAVIORAL ELEMENT TO CORRECT LONG-TERM INHALER TECHNIQUES: Patients who consciously make an effort to perfect asthma inhaler technique will maintain their skills long-term. Elizabeth Azzi at the University of Sydney, Australia, and co-workers further add evidence that there is a strong behavioral component to patients retaining correct inhaler technique over time. Poor inhaler technique can limit asthma control, affecting quality of life and increasing the chances of severe exacerbations. Azzi's team followed 238 patients to determine the key predictors of inhaler technique maintenance from factors including age, asthma knowledge and perceived future risks. Correct inhaler technique at initial assessment was the strongest predictor of long-term success, but this was strengthened further when patients reported good adherence to their own medication regimen. This suggests that maintaining correct inhaler technique is more than just a physical skill. Careful guidance towards this 'practice makes perfect' approach may improve patients' long-term technique maintenance.

The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

PubMed

Nakayama, Kazuhiko; Emoto, Noriaki; Tamada, Naoki; Okano, Mitsumasa; Shinkura, Yuto; Yanaka, Kenichi; Onishi, Hiroyuki; Hiraishi, Mana; Yamada, Shinichiro; Tanaka, Hidekazu; Shinke, Toshiro; Hirata, Ken-Ichi

2018-01-01

Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

PubMed

Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

2017-02-09

Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized labels on asthma inhalers remind patients of correct technique and help improve symptoms over time. Iman Basheti at the Applied Science Private University in Jordan and co-workers trialed the approach of placing patient-specific reminder labels on dry-powder asthma inhalers to improve long-term technique. Poor asthma control is often exacerbated by patients making mistakes when using their inhalers. During the trial, 95 patients received inhaler training before being split into two groups: the control group received no further help, while the other group received individualized labels on their inhalers reminding them of their initial errors. After three months, 67% of patients with reminder labels retained correct technique compared to only 12% of controls. They also required less reliever medication and reported improved symptoms. This represents a simple, cheap way of tackling inhaler technique errors.

Assessing fullness of asthma patients' aerosol inhalers.

PubMed Central

Rickenbach, M A; Julious, S A

1994-01-01

BACKGROUND. The importance of regular medication in order to control asthma symptoms is recognized. However, there is no accurate mechanism for assessing the fullness of aerosol inhalers. The contribution to asthma morbidity of unexpectedly running out of inhaled medication is unknown. AIM. A study was undertaken to determine how patients assess inhaler fullness and the accuracy of their assessments, and to evaluate the floatation method of assessing inhaler fullness. METHOD. An interview survey of 98 patients (51% of those invited to take part), using 289 inhalers, was completed at one general practice in Hampshire. RESULTS. One third of participants said they had difficulty assessing aerosol inhaler fullness and those aged 60 years and over were found to be more inaccurate in assessing fullness than younger participants. Shaking the inhaler to feel the contents move was the commonest method of assessment. When placed in water, an inhaler canister floating on its side with a corner of the canister valve exposed to air indicates that the canister is less than 15% full (sensitivity 90%, specificity 99%). CONCLUSION. Floating a canister in water provides an objective measurement of aerosol inhaler fullness. Providing the method is recommended by the aerosol inhaler manufacturer, general practitioners should demonstrate the floatation method to patients experiencing difficulty in assessing inhaler fullness. PMID:7619099

How to match the optimal currently available inhaler device to an individual child with asthma or recurrent wheeze.

PubMed

van Aalderen, Wim M; Garcia-Marcos, Luis; Gappa, Monika; Lenney, Warren; Pedersen, Søren; Dekhuijzen, Richard; Price, David

2015-01-08

Inhaled medications are the cornerstone of treatment in early childhood wheezing and paediatric asthma. A match between patient and device and a correct inhalation technique are crucial for good asthma control. The aim of this paper is to propose an inhaler strategy that will facilitate an inhaler choice most likely to benefit different groups of children. The main focus will be on pressurised metered dose inhalers and dry powder inhalers. In this paper we will discuss (1) practical difficulties with the devices and with inhaled therapy and (2) the optimal location for deposition of medicines in the lungs, and (3) we will propose a practical and easy way to make the best match between the inhaler device and the individual patient. We hope that this paper will contribute to an increased likelihood of treatment success and improved adherence to therapy.

Is the 'blue' colour convention for inhaled reliever medications important? A UK-based survey of healthcare professionals and patients with airways disease.

PubMed

Fletcher, Monica; Scullion, Jane; White, John; Thompson, Bronwen; Capstick, Toby

2016-11-03

In many countries, short-acting β 2 -agonist inhalers have traditionally been coloured blue. This inhaled therapy has also conventionally been known as a 'reliever' by patients and healthcare professionals (HCPs), in comparison with 'preventer' medications (inhaled steroids). With the rapidly changing market in inhaled therapy for COPD and asthma and growing numbers of devices, there has been some concern that the erosion of traditional colour conventions is leading to patients (and HCPs) becoming confused about the role of different therapies. In order to assess whether there was concern over the perceived changing colour conventions, the UK Inhaler Group carried out a large online survey of patients and HCPs. The aim was to determine how patients and HCPS identify and describe inhaled drugs, and how this might impact on use of medicines and safety. The results of the survey highlighted the importance of the term 'blue inhaler' for patients with only 11.3% never referring to the colour when referring to their inhaler. For HCPs, 95% felt colour conventions were important when referring to reliever medication. In addition, HCPs appear to refer to inhalers mainly by colour when talking to patients. Our conclusions were that the concept of a 'blue inhaler' remains important to patients and healthcare professionals. These results add to the debate about the need to formalise the colour coding of inhaled therapies, in particular using the colour blue for inhalers for rapid relief of symptoms, as this convention may be an important measure and contributor to patient safety. Our survey should provide impetus for all interested parties to discuss and agree a formal industry-wide approach to colour coding of inhaled therapies for the benefit of patients and carers and HCPs.

Nasal inhalation of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in the model of chronic constriction injury to the sciatic nerve of rat.

PubMed

Chen, Feng; Wang, LiQin; Chen, ShuJun; Li, ZhiGao; Chen, ZhouLin; Zhou, XinHua; Zhai, Dong

2014-01-01

The aim of the present study is to explore the impact of butorphanol in combination with ketamine via nasal inhalation (NI) on neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve in a rat model. CCI rats (n = 12) were equally randomized to four groups based on the treatments received as follows: 100 μL of 0.9% normal saline via NI (NS/NI group); 100 μg of butorphanol plus 1 mg of ketamine via NI (B + K/NI group); 100 μg of butorphanol alone via NI (B/NI group); and 100 μg of butorphanol plus 1 mg of ketamine via subcutaneous injection (B + K/SC group). Mechanical pain threshold was measured at 10 min, 30 min, 2 h, 4 h, and 6 h after drug administration. The mechanical pain threshold in the B + K/NI group was improved significantly 4 h after drug administration as compared with that in the B/NI or B + K/SC group (P < 0.05). The onset and intensity of drug action in the B + K/NI group were better than those of the other two groups, but the duration of drug action was not prolonged. NI of butorphanol in combination with ketamine quickly elevates the mechanical pain threshold in a rat neuropathic pain model induced by CCI to the sciatic nerve. Copyright © 2014 Elsevier Inc. All rights reserved.

Customizing inhaled therapy to meet the needs of COPD patients.

PubMed

Fromer, Leonard; Goodwin, Elizabeth; Walsh, John

2010-03-01

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation resulting from emphysema and chronic bronchitis. Inhaled therapy is the major therapeutic approach for treating COPD. Multiple inhaler medications are available in the United States and are delivered by a variety of different devices: metered-dose inhalers, dry powdered inhalers, and nebulizers. Each inhaler device has unique requirements for use that must be correctly performed by the patient for successful drug delivery. Patients with COPD represent a medically diverse population, with each patient having distinct characteristics, such as lung function, comorbidities, cognitive functions, hand strength, and lifestyle. These characteristics impact the patient's ability to properly use specific inhaler devices and therefore affect adherence to therapy, therapeutic outcomes, and quality of life. It is estimated that between 28% to 68% of patients do not use metered-dose inhalers or dry powder inhalers correctly. Worsening symptoms or increased frequency of exacerbations may not always indicate disease progression but may indicate a patient's inability to use their inhaler device properly. This review discusses the patient- and device-specific factors to be considered when choosing an inhaled therapy, which will be concordant with the patient's medical needs, preferences, and lifestyle. The review also considers how the ideas underlying the patient-centered medical home model can be incorporated into the choice and use of inhaler device for a given patient with COPD to improve treatment outcomes.

Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares

PubMed Central

Li, Ning; Harkema, Jack R.; Lewandowski, Ryan P.; Wang, Meiying; Bramble, Lori A.; Gookin, Glenn R.; Ning, Zhi; Kleinman, Michael T.; Sioutas, Constantinos

2010-01-01

We have previously demonstrated that intranasal administration of ambient ultrafine particles (UFP) acts as an adjuvant for primary allergic sensitization to ovalbumin (OVA) in Balb/c mice. It is important to find out whether inhaled UFP exert the same effect on the secondary immune response as a way of explaining asthma flares in already-sensitized individuals due to traffic exposure near a freeway. The objective of this study is to determine whether inhalation exposure to ambient UFP near an urban freeway could enhance the secondary immune response to OVA in already-sensitized mice. Prior OVA-sensitized animals were exposed to concentrated ambient UFP at the time of secondary OVA challenge in our mobile animal laboratory in Los Angeles. OVA-specific antibody production, airway morphometry, allergic airway inflammation, cytokine gene expression, and oxidative stress marker were assessed. As few as five ambient UFP exposures were sufficient to promote the OVA recall immune response, including generating allergic airway inflammation in smaller and more distal airways compared with the adjuvant effect of intranasally instilled UFP on the primary immune response. The secondary immune response was characterized by the T helper 2 and IL-17 cytokine gene expression in the lung. In summary, our results demonstrated that inhalation of prooxidative ambient UFP could effectively boost the secondary immune response to an experimental allergen, indicating that vehicular traffic exposure could exacerbate allergic inflammation in already-sensitized subjects. PMID:20562226

An investigation of fibrogenic and other toxic effects of arc-welding fume particles deposited in the rat lung.

PubMed

Hicks, R; Al-Shamma, K J; Lam, H F; Hewitt, P J

1983-12-01

Lung burdens of deposited particles from fumes generated by arc-welding were established in rats by single inhalation exposures, repeated intermittent exposure or by intratracheal injection. Fumes from manual metal arc-welding using flux-coated mild-steel rods (MMA-MS) were compared with those from metal inert-gas welding with stainless steel wire (MIG-SS). After initial rapid clearance of deposited material from the lungs, persistent residual deposits remained. Such residues resulting from single inhalation were small and confined mainly to peribronchial accumulations in macrophage clusters. Deposits remaining after repeated inhalation were larger and more widespread. Intratracheal administration (50 mg) established massive residual deposits, giving nodular accumulations in peribronchial, subpleural and perivascular sites, with substantial alveolar parenchymal involvement. Deposits from both types of fumes contained predominantly iron. Particles from stainless steel also contained chromium, but concentrations of this element were low in deposits from MMA-MS fumes. MMA-MS deposits contained silica, probably amorphous. Long-term studies (up to 450 days) attempted to detect evidence of fibrosis resulting from particle burdens. Low-grade collagen fibre layers developed at margins of MMA-MS nodules. Diffuse reticulin fibre networks occurred within MIG-SS aggregates. Tissue hydroxyproline levels were increased (doubled) in lungs with intratracheal burdens of MMA-MS particles, but no significant increases resulted from MIG-SS. The major lesions were nodular aggregates of particle-laden macrophages with giant-cell formation, and alveolar epithelial thickening with atelectasis.

Methoxyflurane: A Review in Trauma Pain.

PubMed

Blair, Hannah A; Frampton, James E

2016-12-01

Methoxyflurane (Penthrox ® ) is a halogenated ether first used clinically as a volatile inhalational anaesthetic. It has been used as an analgesic in Australia and New Zealand for the past 30 years. In the UK and Europe, methoxyflurane has been approved for the emergency relief of moderate to severe trauma pain in conscious adult patients. Methoxyflurane is self-administered using a hand-held inhaler. This article reviews the pharmacological properties of methoxyflurane and its clinical efficacy and tolerability in these patients. In the phase III STOP! trial, methoxyflurane was effective and generally well tolerated for the management of acute pain due to minor trauma, with a rapid onset of analgesia. In a prospective study, methoxyflurane was more effective than intramuscular tramadol when administered for the treatment of acute musculoskeletal pain in the pre-hospital setting (i.e. by paramedics). Methoxyflurane had a more rapid onset of action than tramadol when administered for the treatment of pain related to ankle injuries in the emergency department. Although methoxyflurane is known to be potentially nephrotoxic at anaesthetic doses, the much lower doses used for pain relief were not associated with nephrotoxicity or an increased risk of renal disease. Inhaled methoxyflurane may offer advantages over other analgesics administered via the intravenous, intramuscular or intranasal routes in terms of its non-invasive self-administration, ease of use and/or rapid onset of action. As such, it is a useful additional treatment option for the management of trauma pain in the pre-hospital or emergency department setting.

Antimalarial activity of the terpene nerolidol.

PubMed

Saito, Alexandre Y; Marin Rodriguez, Adriana A; Menchaca Vega, Danielle S; Sussmann, Rodrigo A C; Kimura, Emília A; Katzin, Alejandro M

2016-12-01

Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Inhalant Use, Abuse, and Dependence among Adolescent Patients: Commonly Comorbid Problems.

ERIC Educational Resources Information Center

Sakai, Joseph T.; Hall, Shannon K.; Mikulich-Gilbertson, Susan K.; Crowley, Thomas J.

2004-01-01

Objective: Little is known about adolescents with DSM-IV-defined inhalant abuse and dependence. The aim of this study was to compare comorbidity among (1) adolescents with inhalant use disorders, (2) adolescents who reported using inhalants without inhalant use disorder, and (3) other adolescent patients drawn from an adolescent drug and alcohol…

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.

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

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

Inhalation Injuries

MedlinePlus

... breathe in toxic substances, such as smoke (from fires), chemicals, particle pollution, and gases. Inhalation injuries can ... of thermal injuries. Over half of deaths from fires are due to inhalation injuries. Symptoms of inhalation ...

A Survey of Inhalant Use Disorders among Delinquent Youth: Prevalence, Clinical Features, and Latent Structure of DSM-IV Diagnostic Criteria

PubMed Central

Howard, Matthew O; Perron, Brian E

2009-01-01

Background Inhalant use is among the most pernicious and poorly understood forms of adolescent substance use. Many youth in the juvenile justice system have used inhalants, but little is known about inhalant use disorders (IUDs) in antisocial youth populations. The purpose of this study was to examine the prevalence, clinical features, and latent structure of DSM-IV IUDs in a state population of antisocial youth. Methods Cross-sectional survey conducted in 2003. Of 740 youth residing in Missouri State Division of Youth Services' (MDYS) residential treatment facilities at the time the study was conducted, 723 (97.7%) completed interviews. Eighty-seven percent were male, with a mean age of 15.5 (SD = 1.2). Nearly 4 in 10 youth (38.5%; n = 279) reported lifetime inhalant use. Youth ranged from very mildly to severely antisocial. Results Of 279 inhalant users, 52 (18.6%) met DSM-IV inhalant abuse criteria and 79 (28.3%) met inhalant dependence criteria. Five of 10 IUD criteria were met by > 10% of the total sample. Latent class analyses demonstrated a substantial concordance between DSM-IV-defined IUDs and an empirically-derived classification based on responses to DSM-IV IUD diagnostic criteria. Conclusion IUDs and constituent criteria were prevalent among youth in the juvenile justice system. Two groups of problem inhalant users were identified, symptomatic users-DSM-IV inhalant abuse and highly symptomatic users-DSM-IV inhalant dependence, which differed primarily in severity of inhalant-related problems. Inhalant screening, prevention and treatment efforts in juvenile justice settings are rarely delivered, but critically needed. PMID:19267939

Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin

PubMed Central

Tahvanainen, Anna; Leskinen, Miia; Koskela, Jenni; Ilveskoski, Erkki; Alanko, Juha; Kähönen, Mika; Kööbi, Tiit; Lehtimäki, Lauri; Moilanen, Eeva; Mustonen, Jukka; Pörsti, Ilkka

2009-01-01

AIMS To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg−1 min−1) or saline infusion, salbutamol (400 µg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet. RESULTS The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (−9.2 ± 2.6%) and augmentation index (−4.0 ± 1.5%) decreased, and heart rate (8.6 ± 2.5%) and cardiac output (8.8 ± 3.1%) increased. L-arginine had no clear effects on supine haemodynamics, but during head-up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (−6.7 ± 1.8%) and augmentation index (−7.4 ± 1.6%), and increased cardiac output (+9.2 ± 2.7%). During head-up tilt, nitroglycerin increased cardiac output (+10.6 ± 5.6%) and heart rate (+40 ± 7.5%), decreased vascular resistance (−7.8 ± 5.8%) and augmentation index (−18.7 ± 3.2%), and prevented the decrease in aortic reflection time. CONCLUSIONS Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L-arginine were observed during the head-up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head-up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright positions. PMID:19660000

EPINEPHRINE OR GV-26 ELECTRICAL STIMULATION REDUCES INHALANT ANESTHESTIC RECOVERY TIME IN COMMON SNAPPING TURTLES (CHELYDRA SERPENTINA).

PubMed

Goe, Alexandra; Shmalberg, Justin; Gatson, Bonnie; Bartolini, Pia; Curtiss, Jeff; Wellehan, James F X

2016-06-01

Prolonged anesthetic recovery times are a common clinical problem in reptiles following inhalant anesthesia. Diving reptiles have numerous adaptations that allow them to submerge and remain apneic for extended periods. An ability to shunt blood away from pulmonary circulation, possibly due to changes in adrenergic tone, may contribute to their unpredictable inhalant anesthetic recovery times. Therefore, the use of epinephrine could antagonize this response and reduce recovery time. GV-26, an acupuncture point with reported β-adrenergic and respiratory effects, has reduced anesthetic recovery times in other species. In this prospective randomized crossover study, six common snapping turtles (Chelydra serpentina) were anesthetized with inhalant isoflurane for 90 min. Turtles were assigned one of three treatments, given immediately following discontinuation of isoflurane: a control treatment (0.9% saline, at 0.1 ml/kg i.m.), epinephrine (0.1 mg/kg i.m.), or acupuncture with electrical stimulation at GV-26. Each turtle received all treatments, and treatments were separated by 48 hr. Return of spontaneous ventilation was 55% faster in turtles given epinephrine and 58% faster in the GV-26 group versus saline (P < 0.001). The times to movement and to complete recovery were also significantly faster for both treatments than for saline (P < 0.02). Treated turtles displayed increases in temperature not documented in the control (P < 0.001). Turtles administered epinephrine showed significantly increased heart rates and end-tidal CO(2) (P < 0.001). No adverse effects were noted in the study animals. The mechanisms of action were not elucidated in the present investigation. Nevertheless, the use of parenteral epinephrine or GV-26 stimulation in the immediate postanesthetic period produces clinically relevant reductions in anesthetic recovery time in common snapping turtle. Further research is necessary to evaluate the effects of concurrent GV-26 and epinephrine administration and to assess responses in other reptilian species.

Effect of inhaled N-acetylcysteine monotherapy on lung function and redox balance in idiopathic pulmonary fibrosis.

PubMed

Muramatsu, Yoko; Sugino, Keishi; Ishida, Fumiaki; Tatebe, Junko; Morita, Toshisuke; Homma, Sakae

2016-05-01

An oxidant-antioxidant imbalance is considered to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Therefore, administration of antioxidants, such as N-acetylcysteine (NAC), may represent a potential treatment option for IPF patients. The aim of this study was to evaluate the effect of inhaled NAC monotherapy on lung function and redox balance in patients with IPF. A retrospective observational study was done, involving 22 patients with untreated early IPF (19 men; mean [±S.D.] age, 71.8 [±6.3]y). At baseline and at 6 and 12 months after initiating inhaled NAC monotherapy, we assessed forced vital capacity (FVC) and measured the levels of total glutathione, oxidized glutathione (GSSG), and the ratio of reduced to oxidized glutathione in whole blood (hereafter referred to as the ratio), and of 8-hydroxy-2'-deoxyguanosine in urine. To evaluate response to treatment, we defined disease progression as a decrease in FVC of ≥5% from baseline and stable disease as a decrease in FVC of <5%, over a period of 6 months. Change in FVC in the stable group at 6 and 12 months were 95±170mL and -70±120mL, while those in the progressive group at 6 and 12 months were -210±80mL, -320±350mL, respectively. The serial mean change in GSSG from baseline decreased as the ratio of reduced to oxidized glutathione increased in patients with stable disease, while it increased as this ratio decreased in patients with progressive disease. Receiver operating characteristic curve analysis revealed that a baseline GSSG level of ≥1.579μM was optimal for identifying treatment responders. Inhaled NAC monotherapy was associated with improved redox imbalance in patients with early IPF. Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Efficacy of Formoterol Fumarate Delivered by Metered Dose Inhaler Using Co-Suspension™ Delivery Technology Versus Foradil® Aerolizer® in Moderate-To-Severe COPD: A Randomized, Dose-Ranging Study.

PubMed

Sethi, Sanjay; Fogarty, Charles; Hanania, Nicola A; Martinez, Fernando J; Rennard, Stephen; Fries, Michael; Orevillo, Chad; Darken, Patrick; St Rose, Earl; Strom, Shannon; Fischer, Tracy; Golden, Michael; Dwivedi, Sarvajna; Reisner, Colin

2016-11-17

Background: Co-Suspension™ Delivery Technology offers a novel pharmaceutical platform for inhaled drug therapy. This randomized, double-blind, placebo-controlled, single-dose study (NCT01349868) evaluated the efficacy of a range of doses for formoterol fumarate (FF) delivered using Co-Suspension delivery technology via a pressurized metered dose inhaler (MDI) versus placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Secondary objectives included determination of non-inferior efficacy and systemic exposure compared with open-label Foradil ® 12 μg (Foradil ® Aerolizer ® ; formoterol fumarate dry powder inhaler). Methods: Patients received each of the 6 study treatments (FF MDI [7.2, 9.6 and 19.2μg], placebo MDI and open-label Foradil ® [12 and 24µg]), separated by 3-10 days. Spirometry was performed 60 and 30 minutes prior to and at regular intervals up to 12 hours post-administration of study drug. The primary outcome measure was the change in forced expiratory volume in 1 second (FEV 1 ) area under the curve between 0 and 12 hours (AUC 0-12 ) relative to test day baseline. Results: A total of 50 patients were randomized to study treatment sequences. All doses of FF MDI demonstrated superiority to placebo ( p <0.0001) and non-inferiority to Foradil ® 12μg, on bronchodilator outcome measures. No serious adverse events were reported during the study. Conclusions: This study demonstrates non-inferiority of bronchodilator response and bioequivalent exposure of FF MDI 9.6μg to Foradil ® 12μg, with both agents exhibiting a similar safety profile in patients with moderate-to-severe COPD. This study supports the selection of FF MDI 9.6µg for further evaluation in Phase III trials.

Fiber inhalability and head deposition in rats and humans. ...

EPA Pesticide Factsheets

Due to their dimensions and long durability, inhaled asbestos fibers clear slowly from lung airways. Retained fibers may injure the epithelium, interact with macrophages, or translocate to the interstitium to result in various respiratory diseases. Therefore, calculations of fiber inhalability, deposition, and retention in respiratory tract regions of both rats and humans are crucial, both to assess the health risk of fiber exposures and to facilitate inferences from rat inhalation studies. Rat inhalation experiments are underway at the EPA and NIEHS. A model of fiber inhalability and initial deposition in the human and rat nasal cavity was developed. Existing models for particles were extended to fibers by replacing particle diameter with an equivalent fiber diameter. Since fiber inhalability into the respiratory tract and deposition in the extra thoracic airways depended mainly on its inertia, equivalent impaction diameters were derived and substituted in expressions for spherical particle diameter to determine fiber inhalability and nasal losses. Fiber impaction diameter depended strongly on its orientation in the air. Highest inhalability was obtained when fibers were aligned perpendicular to the flow streamlines in the inhaled air. However, detailed calculations of fiber transport in slow moving air such as that in the atmosphere and in lung airways showed that fibers stayed primarily aligned (parallel) to the flow. Therefore, for inhalability calculations,

Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique.

PubMed

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

2008-07-01

To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients. Thirty-one pharmacists received brief workshop education (Active: n=16, CONTROL: n=15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months. At baseline, patients (Active: 53, CONTROL: 44) demonstrated poor inhaler technique (mean+/-S.D. score out of 9, 5.7+/-1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. CONTROL patients (2.8+/-1.6 cf. 0.9+/-1.4, p<0.001), and asthma severity was significantly improved (p=0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient-pharmacist relationship. A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes. Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.

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

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

2014-01-01

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. 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. 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. These data, obtained in an inhalation device-naïve population, suggest that the ELLIPTA DPI is preferred to an established alternative based on its ease-of-use features and is associated with fewer handling errors.

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Pulmonary Hypertension.

PubMed

Kim, John S; McSweeney, Julia; Lee, Joanne; Ivy, Dunbar

2016-03-01

To review the pharmacologic treatment options for pulmonary arterial hypertension in the cardiac intensive care setting and summarize the most-recent literature supporting these therapies. Literature search for prospective studies, retrospective analyses, and case reports evaluating the safety and efficacy of pulmonary arterial hypertension therapies. Mechanisms of action and pharmacokinetics, treatment recommendations, safety considerations, and outcomes for specific medical therapies. Specific targeted therapies developed for the treatment of adult patients with pulmonary arterial hypertension have been applied for the benefit of children with pulmonary arterial hypertension. With the exception of inhaled nitric oxide, there are no pulmonary arterial hypertension medications approved for children in the United States by the Food and Drug Administration. Unfortunately, data on treatment strategies in children with pulmonary arterial hypertension are limited by the small number of randomized controlled clinical trials evaluating the safety and efficacy of specific treatments. The treatment options for pulmonary arterial hypertension in children focus on endothelial-based pathways. Calcium channel blockers are recommended for use in a very small, select group of children who are responsive to vasoreactivity testing at cardiac catheterization. Phosphodiesterase type 5 inhibitor therapy is the most-commonly recommended oral treatment option in children with pulmonary arterial hypertension. Prostacyclins provide adjunctive therapy for the treatment of pulmonary arterial hypertension as infusions (IV and subcutaneous) and inhalation agents. Inhaled nitric oxide is the first-line vasodilator therapy in persistent pulmonary hypertension of the newborn and is commonly used in the treatment of pulmonary arterial hypertension in the ICU. Endothelin receptor antagonists have been shown to improve exercise tolerance and survival in adult patients with pulmonary arterial hypertension. Soluble guanylate cyclase stimulators are the first drug class to be Food and Drug Administration approved for the treatment of chronic thromboembolic pulmonary hypertension. Literature and data supporting the safe and effective use of pulmonary arterial hypertension therapies in children in the cardiac intensive care are limited. Extrapolation of adult data has afforded safe medical treatment of pulmonary hypertension in children. Large multicenter trials are needed in the search for safe and effective therapy of pulmonary hypertension in children.

Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact.

PubMed

Yang, Tian; Wang, Jinyuan; Pang, Yamei; Dang, Xiaomin; Ren, Hui; Liu, Ya; Chen, Mingwei; Shang, Dong

2016-11-01

Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation‑induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice. Emodin and or the sirtuin 1 (Sirt1) inhibitor, nicotinamide, were used to treat the modeled animals. Pulmonary function was assessed using an occlusion method. The deposition of collagen I and α‑smooth muscle actin (SMA) in the lung tissue were detected using fluorescence staining; transforming growth factor‑β1 (TGF‑β1) in the bronchoalveolar lavage fluid (BALF) was examined using an enzyme‑linked immunosorbent assay; TGF-β1/Sirt1/small mothers against decapentaplegic (Smad) signaling activation in lung tissue was also examined. The molecular contacts between emodin were evaluated using liquid chromatography‑mass spectrometry analysis. The deposition of collagen I and α‑SMA in lung tissues were found to be elevated following silica exposure, however, this was relieved by emodin treatment. The pulmonary function of the animals was impaired by silica inhalation, and this was improved by emodin administration. However, the therapeutic effects of emodin on lung fibrosis were impaired by nicotinamide administration. The levels of TGF‑β1 in the BALF and lung tissue were elevated by silica inhalation, however, they were not affected by either emodin or nicotinamide treatment. Additionally, emodin was found to increase the expression level of Sirt1, which decreased the level of deacetylated Smad3 to attenuate collagen deposition. Furthermore, the data suggested that there was direct binding between emodin and Sirt1. Sirt1‑regulated TGF‑β1/Smad signaling was involved in silica inhalation‑induced lung fibrosis. Emodin attenuated this lung fibrosis to improve pulmonary function by targeting Sirt1, which regulated TGF-β1/Smad fibrotic signaling.

Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry

EPA Pesticide Factsheets

EPA's methodology for estimation of inhalation reference concentrations (RfCs) as benchmark estimates of the quantitative dose-response assessment of chronic noncancer toxicity for individual inhaled chemicals.

INFLUENCE OF INHALATION INJURY ON ENERGY EXPENDITURE IN SEVERELY BURNED CHILDREN

PubMed Central

Przkora, Rene; Fram, Ricki Y.; Herndon, David N.; Suman, Oscar E.; Mlcak, Ronald P.

2014-01-01

Objective Determine the effect of inhalation injury on burn-induced hypermetabolism in children. Design Prospective study comparing hypermetabolism (i.e., resting energy expenditure and oxygen consumption) in burned children with and without inhalation injury during acute hospitalization. Setting Single pediatric burn center. Patients Eighty-six children (1–18 years) with ≥ 40% total body surface area burns were stratified to two groups: no inhalation injury and inhalation injury. Interventions None. Main Measurements and Results Inhalation injury was diagnosed based on bronchoscopic evaluation. At admission, PaO2:FiO2 ratios (an index of respiratory distress) were significantly higher in patients with no inhalation injury than in patient with inhalation injury. No differences were detected in resting energy expenditure or percent of the predicted basal metabolic rate between groups. Additionally, oxygen consumption did not significantly differ between groups. Conclusions Inhalation injury does not augment the burn-induced hypermetabolic stress response in children, as reflected by resting energy expenditure and oxygen consumption. PMID:24893760

Supraventricular tachycardia after fenoterol inhalation: report of two cases.

PubMed

Hung, Yu-Fa; Yang, Winnie; Chang, Mei-Ling

2003-01-01

Supraventricular tachycardia (SVT) following fenoterol inhalation in metered-dose inhaler (MDI) has never been reported. We report two cases of SVT after fenoterol inhalation in MDI. Case one was a 4-year-old boy who had asthma since early childhood. Paroxysmal supraventricular tachycardia (PSVT) was found after fenoterol inhalation (MDI), which returned to normal sinus rhythm following adenosine injection. The other one was a 9-year-old male who also had asthma since early childhood. He suffered from attacks of PSVT four times after fenoterol inhalation within one year. After verapamil injection and vagal maneuvers, PSVT was converted to normal sinus rhythm. There were no other episodes of SVT after discontinuing usage of fenoterol inhalation for 2 years in the follow-up. We report these two cases to remind pediatricians that cardiac arrhythmias should be evaluated following fenoterol inhalation (MDI).

The Pharmacokinetics and Biodistribution of a 64 kDa PolyPEG Star Polymer After Subcutaneous and Pulmonary Administration to Rats.

PubMed

Khor, Song Yang; Hu, Jinming; McLeod, Victoria M; Quinn, John F; Porter, Christopher J H; Whittaker, Michael R; Kaminskas, Lisa M; Davis, Thomas P

2016-01-01

PolyPEG star polymers have potential utility as cost-effective polymeric drug delivery vehicles, and as such, it is important to develop an understanding of their biopharmaceutical behavior. Moreover, although a number of studies have evaluated the utility of PolyPEG stars in vitro, investigation of these novel materials in vivo has been limited. Herein, we evaluated the pharmacokinetics of a 64 kDa tritiated PEG-based star polymer after subcutaneous and pulmonary administration in rats. After subcutaneous administration, the star polymer showed near complete bioavailability (∼80%) and a similar organ biodistribution profile to the polymer after intravenous administration. After intratracheal instillation to the lungs, the star polymer showed limited bioavailability (∼3%), and most of the administered radiolabel was recovered in lung tissue and feces after 6 d. The data reported here suggest that star polymers display similar pharmaceutical behavior to PEGylated dendrimers after subcutaneous and inhaled delivery and may therefore be used as similar, but more cost-effective drug delivery vehicles. Copyright © 2016. Published by Elsevier Inc.

"...you would probably want to do it. Cause that's what made them popular": Exploring perceptions of inhalant utility among young adolescent nonusers and occasional users.

PubMed

Siegel, Jason T; Alvaro, Eusebio M; Patel, Neil; Crano, William D

2009-01-01

With an eye toward future primary prevention efforts, this study explores perceptions of inhalant utility among young adolescents in the United States. The study makes use of data gathered via nine focus groups conducted in Tucson, Arizona in 2004 (N = 47, mean age = 13.2 years). Three main themes emerged concerning the perceived utility of inhalant use: (1) Inhalant use as a means of mental escape, (2) Inhalant use as a social tool, and (3) Inhalant use as a parental relations tool. Additionally, participants discussed an interaction hypothesis regarding inhalant use and popularity. Implications for future research are suggested and limitations described.

49 CFR 172.400 - General labeling requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 172.411 1.6 EXPLOSIVES 1.6 172.411 2.1 FLAMMABLE GAS 172.417 2.2 NONFLAMMABLE GAS 172.415 2.3 POISON...)) POISON INHALATION HAZARD 172.429 6.1(other than material poisonous by inhalation) POISON 172.430 6.1 (inhalation hazard, Zone A or B) POISON INHALATION HAZARD 172.429 6.1 (other than inhalation hazard, Zone A or...

49 CFR 172.400 - General labeling requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 172.411 1.6 EXPLOSIVES 1.6 172.411 2.1 FLAMMABLE GAS 172.417 2.2 NONFLAMMABLE GAS 172.415 2.3 POISON...)) POISON INHALATION HAZARD 172.429 6.1(other than material poisonous by inhalation) POISON 172.430 6.1 (inhalation hazard, Zone A or B) POISON INHALATION HAZARD 172.429 6.1 (other than inhalation hazard, Zone A or...

49 CFR 172.400 - General labeling requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 172.411 1.6 EXPLOSIVES 1.6 172.411 2.1 FLAMMABLE GAS 172.417 2.2 NONFLAMMABLE GAS 172.415 2.3 POISON...)) POISON INHALATION HAZARD 172.429 6.1(other than material poisonous by inhalation) POISON 172.430 6.1 (inhalation hazard, Zone A or B) POISON INHALATION HAZARD 172.429 6.1 (other than inhalation hazard, Zone A or...

49 CFR 172.400 - General labeling requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 172.411 1.6 EXPLOSIVES 1.6 172.411 2.1 FLAMMABLE GAS 172.417 2.2 NONFLAMMABLE GAS 172.415 2.3 POISON...)) POISON INHALATION HAZARD 172.429 6.1(other than material poisonous by inhalation) POISON 172.430 6.1 (inhalation hazard, Zone A or B) POISON INHALATION HAZARD 172.429 6.1 (other than inhalation hazard, Zone A or...

49 CFR 172.400 - General labeling requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 172.411 1.6 EXPLOSIVES 1.6 172.411 2.1 FLAMMABLE GAS 172.417 2.2 NONFLAMMABLE GAS 172.415 2.3 POISON...)) POISON INHALATION HAZARD 172.429 6.1(other than material poisonous by inhalation) POISON 172.430 6.1 (inhalation hazard, Zone A or B) POISON INHALATION HAZARD 172.429 6.1 (other than inhalation hazard, Zone A or...

Objective Assessment of Patient Inhaler User Technique Using an Audio-Based Classification Approach.

PubMed

Taylor, Terence E; Zigel, Yaniv; Egan, Clarice; Hughes, Fintan; Costello, Richard W; Reilly, Richard B

2018-02-01

Many patients make critical user technique errors when using pressurised metered dose inhalers (pMDIs) which reduce the clinical efficacy of respiratory medication. Such critical errors include poor actuation coordination (poor timing of medication release during inhalation) and inhaling too fast (peak inspiratory flow rate over 90 L/min). Here, we present a novel audio-based method that objectively assesses patient pMDI user technique. The Inhaler Compliance Assessment device was employed to record inhaler audio signals from 62 respiratory patients as they used a pMDI with an In-Check Flo-Tone device attached to the inhaler mouthpiece. Using a quadratic discriminant analysis approach, the audio-based method generated a total frame-by-frame accuracy of 88.2% in classifying sound events (actuation, inhalation and exhalation). The audio-based method estimated the peak inspiratory flow rate and volume of inhalations with an accuracy of 88.2% and 83.94% respectively. It was detected that 89% of patients made at least one critical user technique error even after tuition from an expert clinical reviewer. This method provides a more clinically accurate assessment of patient inhaler user technique than standard checklist methods.

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.

Elemental properties of copper slag and measured airborne exposures at a copper slag processing facility.

PubMed

Mugford, Christopher; Gibbs, Jenna L; Boylstein, Randy

2017-08-01

In 1974, the National Institute for Occupational Safety and Health recommended a ban on the use of abrasives containing >1% silica, giving rise to abrasive substitutes like copper slag. We present results from a National Institute for Occupational Safety and Health industrial hygiene survey at a copper slag processing facility that consisted of the collection of bulk samples for metals and silica; and full-shift area and personal air samples for dust, metals, and respirable silica. Carcinogens, suspect carcinogens, and other toxic elements were detected in all bulk samples, and area and personal air samples. Area air samples identified several areas with elevated levels of inhalable and respirable dust, and respirable silica: quality control check area (236 mg/m 3 inhalable; 10.3 mg/m 3 respirable; 0.430 mg/m 3 silica), inside the screen house (109 mg/m 3 inhalable; 13.8 mg/m 3 respirable; 0.686 mg/m 3 silica), under the conveyor belt leading to the screen house (19.8 mg/m 3 inhalable), and inside a conveyor access shack (11.4 mg/m 3 inhalable; 1.74 mg/m 3 respirable; 0.067 mg/m 3 silica). Overall, personal dust samples were lower than area dust samples and did not exceed published occupational exposure limits. Silica samples collected from a plant hand and a laborer exceeded the American Conference of Governmental Industrial Hygienist Threshold Limit Value of 0.025 µg/m 3 . All workers involved in copper slag processing (n = 5) approached or exceeded the Occupational Safety and Health Administration permissible exposure limit of 10 µg/m 3 for arsenic (range: 9.12-18.0 µg/m 3 ). Personal total dust levels were moderately correlated with personal arsenic levels (R s = 0.70) and personal respirable dust levels were strongly correlated with respirable silica levels (R s = 0.89). We identified multiple areas with elevated levels of dust, respirable silica, and metals that may have implications for personal exposure at other facilities if preventive measures are not taken. To our knowledge, this is the first attempt to characterize exposures associated with copper slag processing. More in-depth air monitoring and health surveillance is needed to understand occupational exposures and health outcomes in this industry.

Respiratory reflexes in spontaneously breathing anesthetized dogs in response to nasal administration of sevoflurane, isoflurane, or halothane.

PubMed

Mutoh, T; Kanamaru, A; Suzuki, H; Tsubone, H; Nishimura, R; Sasaki, N

2001-03-01

To characterize respiratory reflexes elicited by nasal administration of sevoflurane (Sevo), isoflurane (Iso), or halothane (Hal) in anesthetized dogs. 8 healthy Beagles. A permanent tracheostomy was created in each dog. Two to 3 weeks later, dogs were anesthetized by IV administration of thiopental and alpha-chloralose. Nasal passages were isolated such that inhalant anesthetics could be administered to the nasal passages while the dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of each anesthetic at 1.2 and 2.4 times the minimum alveolar concentration (MAC) and the full vaporizer setting (5%) were recorded. Reflexes in response to administration of 5% of each anesthetic also were recorded following administration of lidocaine to the nasal passages. Nasal administration of Sevo, Iso, and Hal induced an immediate ventilatory response characterized by a dose-dependent increase in expiratory time and a resulting decrease in expired volume per unit of time. All anesthetics had a significant effect, but for Sevo, the changes were smaller in magnitude. Responses to administration of each anesthetic were attenuated by administration of lidocaine to the nasal passages. Nasal administration of Sevo at concentrations generally used for mask induction of anesthesia induced milder reflex inhibition of breathing, presumably via afferent neurons in the nasal passages, than that of Iso or Hal. Respiratory reflexes attributable to stimulation of the nasal passages may contribute to speed of onset and could promote a smoother induction with Sevo, compared with Iso or Hal.

How to use an inhaler - with spacer

MedlinePlus

... MDIs) usually have 3 parts: A mouthpiece A cap that goes over the mouthpiece A canister full ... Take the cap off the inhaler and spacer. Shake the inhaler hard. Attach the spacer to the inhaler. If you have ...

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...

MODELING DEPOSITION OF INHALED PARTICLES

EPA Science Inventory

Modeling Deposition of Inhaled Particles: ABSTRACT

The mathematical modeling of the deposition and distribution of inhaled aerosols within human lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental aerosols and the therapeut...

IRIS Toxicological Review of Vanadium Pentoxide ...

EPA Pesticide Factsheets

On September 30, 2011, the draft Toxicological Review of Vanadium Pentoxide and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process (May 2009), introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Vanadium Pentoxide and the charge to external peer reviewers are posted on this site. EPA is reassessing its IRIS toxicological review of vanadium pentoxide (CASRN 1314-62-1). This vanadium pentoxide reassessment consists of an oral reference dose (RfD), an inhalation reference concentration (RfC), an inhalation unit risk (IUR) and a cancer weight of evidence descriptor. This is the first assessment developing an RfC or IUR for this compound. This assessment is intended to provide human health data to support agency regulatory decisions.

A Novel Method for Studying the Pharmacokinetics of [14C]Umeclidinium After Application to the Axilla or Palm of Healthy Male Subjects

PubMed Central

Santos, LL; Hughes, SC; Pereira, AI; Young, GC; Hussey, E; Charlton, P; Baptiste‐Brown, S; Stuart, JS; Vincent, V; van Marle, SP; Schmith, VD

2016-01-01

Umeclidinium (UMEC), a long‐acting muscarinic antagonist approved for chronic obstructive pulmonary disease (COPD), was investigated for primary hyperhidrosis as topical therapy. This study evaluated the pharmacokinetics, safety, and tolerability of a single dose of [14C]UMEC applied to either unoccluded axilla (UA), occluded axilla (OA), or occluded palm (OP) of healthy males. After 8 h the formulation was removed. [14C]UMEC plasma concentrations (Cp) were quantified by accelerator mass spectrometry. Occlusion increased systemic exposure by 3.8‐fold. Due to UMEC absorption‐limited pharmacokinetics, Cp data from the OA were combined with intravenous data from a phase I study. The data were described by a two‐compartment population model with sequential zero and first‐order absorption and linear elimination. Simulated systemic exposure following q.d. doses to axilla was similar to the exposure from the inhaled therapy, suggesting that systemic safety following dermal administration can be bridged to the inhaled program, and offering the potential for a reduced number of studies and/or subjects. PMID:27304394

Age of Inhalant First Time Use and Its Association to the Use of Other Drugs

ERIC Educational Resources Information Center

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

2009-01-01

Inhalants are the 4th most commonly abused drugs after alcohol, tobacco, and marijuana. Although inhalants are often referred as Gateway Drugs this hypothesis is less examined. Using the 2003 National Survey on Drug Use and Health data, age of first time inhalant use was compared with the age of onset of other drugs among 6466 inhalant users who…

Skills in Handling Turbuhaler, Diskus, and Pressurized Metered-Dose Inhaler in Korean Asthmatic Patients

PubMed Central

Lee, Sang Min; Chang, Yoon-Seok; Kim, Cheol-Woo; Kim, Tae-Bum; Kim, Sang-Heon; Kwon, Yong-Eun; Lee, Jong-Myung; Lee, Soo-Keol; Jeong, Jae-Won; Park, Jung-Won; Cho, Sang-Heon; Moon, Hee-Bom

2011-01-01

Purpose The objective of this study was to evaluate skills in handling inhalers and factors associated with these skills among patients with asthma who had undergone treatment at special asthma and allergy clinics in Korea. Methods We enrolled 78 subjects who used Turbuhaler and 145 who used Diskus for asthma control at special clinics in 10 university hospitals and visually assessed their skills in handling these inhalers. We also evaluated skills in 137 subjects who had used pressurized metered-dose inhalers (pMDIs) for symptom relief. Age, sex, duration of asthma and inhaler use, smoking status, monthly income, highest grade completed in school and previous instruction for handling inhalers were also measured to evaluate their association with overall inhaler skills. Results Performance grade was inadequate for 12.8% of participants using Turbuhaler, 6.2% for Diskus, and 23.4% for pMDIs. The success rates for each step in handling the inhalers were relatively high except for the "exhale slowly to residual volume" step, in which success rates ranged from 24.2% to 28.5%. Older age, male sex, lower educational grade, and absence of previous instruction for handling inhalers were associated with inadequate inhaler technique in univariate analysis; however, only older age and absence of previous instruction remained significant independent risk factors in multivariate analysis. Conclusions Among Korean asthmatic patients in special asthma and allergy clinics, skills in handling their inhalers were mostly excellent; meanwhile, older age and absence of previous instruction for handling inhalers were associated with inadequate techniques. PMID:21217925

Exploring the role of quantitative feedback in inhaler technique education: a cluster-randomised, two-arm, parallel-group, repeated-measures study.

PubMed

Toumas-Shehata, Mariam; Price, David; Basheti, Iman Amin; Bosnic-Anticevich, Sinthia

2014-11-13

Feedback is a critical component of any educational intervention. When it comes to feedback associated with inhaler technique education, there is a lack of knowledge on its role or its potential to solve the major issue of poor inhaler technique. This study aims to explore the role of feedback in inhaler technique education and its impact on the inhaler technique of patients over time. A parallel-group, repeated-measures study was conducted in the community pharmacy in which the effectiveness of current best practice inhaler technique education utilising qualitative visual feedback (Group 1) was compared with a combination of qualitative and quantitative visual feedback (Group 2). The impact of these two interventions on inhaler technique maintenance was evaluated. Community pharmacists were randomly allocated to recruit people with asthma who were using a dry powder inhaler. At Visit 1 their inhaler technique was evaluated and education delivered and they were followed up at Visit 2 (1 month later). Both educational interventions resulted in an increase in the proportion of patients with correct inhaler technique: from 4% to 51% in Group 1 and from 6% to 83% in Group 2 (Pearson's Chi-Squared, P=0.03, n=49, and Pearson's Chi-Squared, P=0.01, n=48, respectively). The magnitude of improvement was statistically significantly higher for Group 2 compared with Group 1 (n=97, P=0.02, Pearson's Chi-Square test). The nature of feedback has an impact on the effectiveness of inhaler technique education with regard to correct inhaler technique maintenance over time.

Nurses' knowledge of inhaler technique in the inpatient hospital setting.

PubMed

De Tratto, Katie; Gomez, Christy; Ryan, Catherine J; Bracken, Nina; Steffen, Alana; Corbridge, Susan J

2014-01-01

High rates of inhaler misuse in patients with chronic obstructive pulmonary disease and asthma contribute to hospital readmissions and increased healthcare cost. The purpose of this study was to examine inpatient staff nurses' self-perception of their knowledge of proper inhaler technique compared with demonstrated technique and frequency of providing patients with inhaler technique teaching during hospitalization and at discharge. A prospective, descriptive study. A 495-bed urban academic medical center in the Midwest United States. A convenience sample of 100 nurses working on inpatient medical units. Participants completed a 5-item, 4-point Likert-scale survey evaluating self-perception of inhaler technique knowledge, frequency of providing patient education, and responsibility for providing education. Participants demonstrated inhaler technique to the investigators using both a metered dose inhaler (MDI) and Diskus device inhaler, and performance was measured via a validated checklist. Overall misuse rates were high for both MDI and Diskus devices. There was poor correlation between perceived ability and investigator-measured performance of inhaler technique. Frequency of education during hospitalization and at discharge was related to measured level of performance for the Diskus device but not for the MDI. Nurses are a key component of patient education in the hospital; however, nursing staff lack adequate knowledge of inhaler technique. Identifying gaps in nursing knowledge regarding proper inhaler technique and patient education about proper inhaler technique is important to design interventions that may positively impact patient outcomes. Interventions could include one-on-one education, Web-based education, unit-based education, or hospital-wide competency-based education. All should include return demonstration of appropriate technique.

3-D SIMULATIONS OF AIRWAYS WITHIN HUMAN LUNGS

EPA Science Inventory

Information regarding the deposition patterns of inhaled particles has important application to the fields of toxicology and medicine. The former concerns the risk assessment of inhaled air pollutants (inhalation toxicology); the latter concerns the targeted delivery of inhaled ...

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-of-use features and is associated with fewer handling errors. PMID:25525354

Study of inhaler technique in asthma patients: differences between pediatric and adult patients

PubMed Central

Manríquez, Pablo; Acuña, Ana María; Muñoz, Luis; Reyes, Alvaro

2015-01-01

Objective: Inhaler technique comprises a set of procedures for drug delivery to the respiratory system. The oral inhalation of medications is the first-line treatment for lung diseases. Using the proper inhaler technique ensures sufficient drug deposition in the distal airways, optimizing therapeutic effects and reducing side effects. The purposes of this study were to assess inhaler technique in pediatric and adult patients with asthma; to determine the most common errors in each group of patients; and to compare the results between the two groups. Methods: This was a descriptive cross-sectional study. Using a ten-step protocol, we assessed inhaler technique in 135 pediatric asthma patients and 128 adult asthma patients. Results: The most common error among the pediatric patients was failing to execute a 10-s breath-hold after inhalation, whereas the most common error among the adult patients was failing to exhale fully before using the inhaler. Conclusions: Pediatric asthma patients appear to perform most of the inhaler technique steps correctly. However, the same does not seem to be true for adult patients. PMID:26578130

Awareness of environmental issues and the acceptance of CFC-free inhalers.

PubMed

Goh, S Y; Arulanandam, S; Ho, C L; Zhang, L; Goh, D Y; Chew, F T; Lee, B W

1998-09-01

With the recent availability of a chlorofluorocarbon (CFC)-free metered dose inhaler (MDI) (Airomir), a patient survey was carried out to evaluate awareness of the role of CFCs in our environment and acceptance of this new inhaler. A questionnaire survey was conducted on parents and guardians of 201 children. Depending on respondents' preference, the interview was conducted in English (71%), Chinese (23%), Malay (5%) or Tamil (1%). A 'taste' test was also conducted on 103 of these children. Only 13% (26/201) of parents/guardians were aware that MDIs contained CFCs. Although 70% of children were in favour of the new taste of the CFC-free inhaler, the cost of the new inhaler was an important consideration for parents and guardians in their decision to switch to the new inhaler. The majority (93%) were willing to switch if its cost were equivalent to their current inhaler. This study has provided pertinent information with regard to acceptance of CFC-free inhalers which should be considered when making the inevitable switch to environmentally friendly inhalers.

Use of nitrite inhalants ("poppers") among American youth.

PubMed

Wu, Li-Tzy; Schlenger, William E; Ringwalt, Chris L

2005-07-01

We examined the patterns and correlates of nitrite inhalant use among adolescents aged 12 to 17 years. Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Logistic regression was used to identify the characteristics associated with nitrite inhalant use. Among adolescents aged 12 to 17 years, 1.5% reported any lifetime use of nitrite inhalants. The prevalence of lifetime nitrite inhalant use increased to 12% and 14% among adolescents who were dependent on alcohol and any drug in the past year, respectively. Many nitrite inhalant users used at least three other types of inhalants (68%) and also met the criteria for alcohol (33%) and drug (35%) abuse or dependence. Increased odds of nitrite inhalant use were associated with residing in nonmetropolitan areas, recent utilization of mental health services, delinquent behaviors, past year alcohol and drug abuse and dependence, and multi-drug use. Adolescents who had used nitrite inhalants at least once in their lifetime tend to engage in delinquent activities and report co-occurring multiple drug abuse and mental health problems in the past year.

Recent developments in the understanding and use of anthrax vaccine adsorbed: achieving more with less.

PubMed

Schiffer, Jarad M; McNeil, Michael M; Quinn, Conrad P

2016-09-01

Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine's PEP application.

Inhalation Injury: State of the Science 2016.

PubMed

Foster, Kevin N; Holmes, James H

This article summarizes research conducted over the last decade in the field of inhalation injury in thermally injured patients. This includes brief summaries of the findings of the 2006 State of the Science meeting with regard to inhalation injury, and of the subsequent 2007 Inhalation Injury Consensus Conference. The reviewed studies are categorized in to five general areas: diagnosis and grading; mechanical ventilation; systemic and inhalation therapy; mechanistic alterations; and outcomes.

Optimizing inhalation technique using web-based videos in obstructive lung diseases.

PubMed

Müller, Tobias; Müller, Annegret; Hübel, Christian; Knipel, Verena; Windisch, Wolfram; Cornelissen, Christian Gabriel; Dreher, Michael

2017-08-01

Inhaled agents are widely used in the treatment of chronic airway diseases. Correct technique is required to ensure appropriate drug deposition, but poor technique is common. This study investigated whether inhalation technique could be improved by patient training using short videos from the German Airway League. Outpatients from a university hospital respiratory clinic who had incorrect inhalation technique were asked to demonstrate this again immediately after viewing the training videos, and after 4-8 weeks' follow-up. Inhalation technique was rated by a study nurse using specific checklists. One hundred and twelve patients with obstructive lung disease treated with inhaled bronchodilators or corticosteroids were included. More than half (51.8%) had at least one mistake in inhalation technique at baseline. Of these, most (88%) understood the training videos, 76% demonstrated correct device use immediately after training, and 72% were still able to demonstrate correct inhalation technique at follow-up (p = 0.0008 for trend). In addition, the number of mistakes decreased significantly after video training (by 1.82 [95% confidence interval 1.39-2.25]; p < 0.0001 vs. baseline). German Airway League inhalation technique training videos were easy to understand and effectively improved inhalation technique in patients with airway diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of respiratory tract disease and mode of inhalation on detectability of budesonide in equine urine and plasma.

PubMed

Barton, Ann Kristin; Heinemann, Henrike; Schenk, Ina; Machnik, Marc; Gehlen, Heidrun

2017-02-01

OBJECTIVE To evaluate the influence of respiratory tract disease (ie, recurrent airway obstruction [RAO]) and mode of inhalation on detectability of inhaled budesonide in equine plasma and urine samples. ANIMALS 16 horses (8 healthy control horses and 8 horses affected by RAO, as determined by results of clinical examination, blood gas analysis, bronchoscopy, and cytologic examination of bronchoalveolar lavage fluid). PROCEDURES 4 horses of each group inhaled budesonide (3 μg/kg) twice daily for 10 days while at rest, and the remaining 4 horses of each group inhaled budesonide during lunging exercise. Plasma and urine samples were obtained 4 to 96 hours after inhalation and evaluated for budesonide and, in urine samples, the metabolites 6β-hydroxybudesonide and 16α-hydroxyprednisolone. RESULTS Detected concentrations of budesonide were significantly higher at all time points for RAO-affected horses, compared with concentrations for the control horses. All samples of RAO-affected horses contained budesonide concentrations above the limit of detection at 96 hours after inhalation, whereas this was found for only 2 control horses. Detected concentrations of budesonide were higher, but not significantly so, at all time points in horses that inhaled budesonide during exercise, compared with concentrations for inhalation at rest. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that the time interval between inhalation of a glucocorticoid and participation in sporting events should be increased when inhalation treatment is administered during exercise to horses affected by respiratory tract disease.

COPD Medicine

MedlinePlus

... Rotahaler® Turbuhaler® Twisthaler® Metered-Dose Inhaler (MDI) HFA Propellant Metered-Dose Inhaler and Spacer AeroChamber® AeroChamber® with ... Rotahaler® Turbuhaler® Twisthaler® Metered-Dose Inhaler (MDI) HFA Propellant Metered-Dose Inhaler and Spacer AeroChamber® AeroChamber® with ...

The Ellipta® in asthma and chronic obstructive pulmonary disease: device characteristics and patient acceptability.

PubMed

Jones, Thomas L; Neville, Daniel M; Chauhan, Anoop J

2018-02-01

Asthma and chronic obstructive pulmonary disease are primarily treated with inhaled medication, but delivery of that medication to its site of action is problematic; patients' ability to use inhalers will affect therapeutic response. Multiple inhaler devices are available but they are variably easy to use with consequent effects on compliance, intentional or otherwise. The Ellipta ® device is a novel blister strip dry powder inhaler with medium resistance and a consistent delivered dose across a range of inspiratory flow rates. The Ellipta has proven easy to use and is preferred by patients across several evaluations and compared with other inhaler devices. The Ellipta is used to administer multiple inhaled medications, all in single daily-dose regimens, making it ideal for patients who struggle with complex inhaled therapy regimens.

Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

PubMed Central

van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

2014-01-01

Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

Protective Immunization Against Inhalational Anthrax: A Comparison of Minimally Invasive Delivery Platforms

DTIC Science & Technology

2004-12-15

278 • JID 2005:191 (15 January) • Mikszta et al. M A J O R A R T I C L E Protective Immunization against Inhalational Anthrax: A Comparison of...provides complete protection against inhalational anthrax in rabbits. The novel vaccine/device combi- nations described here have the potential to...have produced documented fatali- ties, the fatality rate of inhalational anthrax is nearly 100% without antibiotic intervention. Inhalational an

Maintenance inhaler preference, attribute importance, and satisfaction in prescribing physicians and patients with asthma, COPD, or asthma–COPD overlap syndrome consulting for routine care

PubMed Central

Ding, Bo; Small, Mark; Scheffel, Gina; Holmgren, Ulf

2018-01-01

Background In respiratory disorders, patient- and physician-perceived satisfaction with the maintenance inhaler device is an important factor driving treatment compliance and outcomes. We examine inhaler preferences in asthma and COPD from patient and physician perspectives, particularly focusing on the relative importance of individual device attributes and patient characteristics guiding inhaler choice. Materials and methods Real-world data from >7,300 patients with asthma, COPD, or asthma–COPD overlap syndrome (ACOS) consulting for routine care were derived from respiratory Disease Specific Programs conducted in Europe, USA, Japan, and China. Outcome variables included current pattern of inhaled maintenance therapy and device type, physician preference, patient-reported device attribute importance, and satisfaction. Results The most commonly prescribed inhalers for maintenance therapy of asthma, COPD, and ACOS were dry powder inhalers (62.8%–88.5% of patients) and pressurized metered dose inhalers (18.9%–35.3% of patients). One-third of physicians stated no preference for maintenance device when prescribing treatment, and less than one-third of patients reported being “extremely satisfied” with any attribute of their device. Instructions being “simple and easy to follow” was the inhaler attribute most commonly selected as important. For approximately one-third of patients across all groups, “ease of use/suitability of inhaler device” was a reason for the prescribing decision, as stated by the physician. Device characteristics were more likely to impact the prescribing decision in older patients (in asthma and COPD; P<0.01) and those with worse disease severity (in COPD; P<0.001). Conclusion A relatively high proportion of physicians had no preference for inhaler type across asthma, COPD, and ACOS. Simplicity of use was the most important inhaler attribute from a patient’s perspective. Physicians appeared to place most importance on ease of use and device suitability when selecting inhalers for older patients and those with more severe disease, particularly in COPD. PMID:29588581

TARGETED DELIVERY OF INHALED PHARMACEUTICALS USING AN IN SILICO DOSIMETRY MODEL

EPA Science Inventory

We present an in silico dosimetry model which can be used for inhalation toxicology (risk assessment of inhaled air pollutants) and aerosol therapy ( targeted delivery of inhaled drugs). This work presents scientific and clinical advances beyond the development of the original in...

A review of the value of innovation in inhalers for COPD and asthma

PubMed Central

Virchow, Johann Christian; Akdis, Cezmi A.; Darba, Josep; Dekhuijzen, Richard; Hartl, Sylvia; Kobelt, Gisela; Roger, Albert; Simoens, Steven; Toumi, Mondher; Woodhouse, Ben; Plich, Adam; Torvinen, Saku

2015-01-01

Background Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. Methods In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. Conclusions The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms. PMID:27123170

A review of the value of innovation in inhalers for COPD and asthma.

PubMed

Virchow, Johann Christian; Akdis, Cezmi A; Darba, Josep; Dekhuijzen, Richard; Hartl, Sylvia; Kobelt, Gisela; Roger, Albert; Simoens, Steven; Toumi, Mondher; Woodhouse, Ben; Plich, Adam; Torvinen, Saku

2015-01-01

Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms.

LPG Dependence after a Suicide Attempt

PubMed Central

Aldemir, Ebru; Akyel, Betül; Altıntoprak, A. Ender; Aydın, Rezzan; Coşkunol, Hakan

2015-01-01

Inhalant abuse is a problem that is getting more common all around the world. The increase in prevalence of inhalant abuse escalates morbidity and mortality rates. About 22% of people using inhalant have died at their first attempt. Particularly propane, butane, or propane-butane mixture has highest mortality rates. Sudden sniffing death syndrome, cardiomyopathy, central nervous system toxicity, hematological abnormalities, kidney toxicity, and hepatocellular toxicities are the major complications of inhalant abuse. Herein we present a patient with inhalant use disorder. At the age of 19, after a stressful life event he had unsuccessfully tried to suicide by inhaling LPG (liquefied petroleum gas, a mixture of butane and propane gases). After he realized that he had hallucinations and felt better during the inhalation, he started to abuse it. He was addicted to LPG for 10 years at the time of admission. Besides being dangerous for the society security, this intense level of LPG inhalation (12 liters a day) not giving any physical harm makes this case interesting. PMID:25664196

[Evaluation of an education program for patients with asthma who use inhalers].

PubMed

Lee, Jong Kyung; Yang, Young Hee

2010-04-01

This study was done to evaluate the effectiveness of an education program for patients with asthma who use inhalers. The research design for this study was a non-equivalent control group quasi-experimental study. Participants in this study were 36 patients for the control group, and 43 patients for the experimental group. The experimental group participated in the education program. The control group received the usual care. Data were collected before and 1 month and 2 months after the program finished and were analyzed using the SPSS 12.0 program. The experimental group had significantly higher scores of knowledge of inhalers, and inhalation technique compared to the control group. However, no significant differences were found between two groups for PEFR, asthma instability, and satisfaction with inhalers. According to the results, the education program was effective in improving knowledge of inhalers, and inhalation technique. Therefore, it is recommended that this education program be used in clinical practice as an effective nursing intervention for patients with asthma on inhalers.

Inhaled antibiotics in non-cystic fibrosis bronchiectasis: A meta-analysis.

PubMed

Xu, Li; Zhang, Fei; Du, Shuai; Yu, Qi; Chen, Lin; Long, Li-Hui; Li, Ya-Ming; Jia, Ai-Hua

2016-09-01

To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.

LPG Dependence after a Suicide Attempt.

PubMed

Aldemir, Ebru; Akyel, Betül; Altıntoprak, A Ender; Aydın, Rezzan; Coşkunol, Hakan

2015-01-01

Inhalant abuse is a problem that is getting more common all around the world. The increase in prevalence of inhalant abuse escalates morbidity and mortality rates. About 22% of people using inhalant have died at their first attempt. Particularly propane, butane, or propane-butane mixture has highest mortality rates. Sudden sniffing death syndrome, cardiomyopathy, central nervous system toxicity, hematological abnormalities, kidney toxicity, and hepatocellular toxicities are the major complications of inhalant abuse. Herein we present a patient with inhalant use disorder. At the age of 19, after a stressful life event he had unsuccessfully tried to suicide by inhaling LPG (liquefied petroleum gas, a mixture of butane and propane gases). After he realized that he had hallucinations and felt better during the inhalation, he started to abuse it. He was addicted to LPG for 10 years at the time of admission. Besides being dangerous for the society security, this intense level of LPG inhalation (12 liters a day) not giving any physical harm makes this case interesting.

Application unit for the administration of contrast gases for pulmonary magnetic resonance imaging: optimization of ventilation distribution for (3) He-MRI.

PubMed

Güldner, M; Becker, St; Wolf, U; Düber, C; Friesenecker, A; Gast, K K; Heil, W; Hoffmann, C; Karpuk, S; Otten, E W; Rivoire, J; Salhi, Z; Scholz, A; Schreiber, L M; Terekhov, M

2015-09-01

MRI of lung airspaces using gases with MR-active nuclei ((3) He, (129) Xe, and (19) F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a (3) He bolus. A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with minimal HP losses). The setup was tested in a clinical trial (n = 10 healthy volunteers) according to the German medicinal products law using static and dynamic ventilation HP-(3) He MRI. The required specifications for the AU were successfully realized. Compared to PB-administration, better reproducibility of gas intrapulmonary distribution was observed when using the AU for both static and dynamic ventilation imaging. The new AU meets the special requirements for HP gases, which are storage and administration with minimal losses. Our data suggest that gas AU-administration is superior to manual modes for determining the key parameters of dynamic ventilation measurements. © 2014 Wiley Periodicals, Inc.

The impact of expired and empty quick-relief asthma inhalers: The Asthma and Allergy Foundation of America's Asthma Inhaler Design Survey.

PubMed

Storms, William W; Tringale, Mike; Ferro, Thomas J

2015-01-01

Despite the available treatments, asthma remains a serious illness, with a considerable socioeconomic burden associated with a high number of unscheduled visits to the emergency department (ED). Poor adherence and inadequate inhaler technique are contributing factors to poor asthma management and control. The Asthma Inhaler Design Survey assessed the behaviors, attitudes, needs, and preferences of patients with asthma and their caregivers with regard to quick-relief inhaler usage and device design. The Asthma and Allergy Foundation of America invited 19,157 adult patients and parents of children with asthma to take part in an online survey that focused on previous asthma diagnosis, symptom severity, and quick-relief and controller medication use. Opinions were also collected. Data from 590 respondents (366 adults; 224 children) were included in the final analysis. Relief inhalers were needed and found to be past the expiration date by 284 of 561 (50.6%) and relief inhalers were found to be empty by 270 of 560 (48.2%). Of the empty inhaler group, 28 of 270 (10.4%) had to visit the ED for treatment, 18 of 270 (6.7%) missed work or school for an unscheduled physician office visit, and 54 of 270 (20%) went without treatment. Although 78.5% indicated that they had at least two quick-relief inhalers nearby, these were not always easily accessible. Few respondents (194/578 [33.6%]) indicated that they and/or their child were very confident that they were using their inhaler properly, even though the majority had received some instruction. When asked what they would do to improve satisfaction with their quick-relief inhalers, 173 of 558 (31%) responded that they would add a dose counter. Unnecessary health care utilization and avoidable loss of time at work or school were associated with the lack of full availability of properly functioning quick-relief inhalers when needed. Adding a dose counter was the most frequently cited response for improving satisfaction with quick-relief inhalers. Confidence about proper inhaler use was low, despite previous instruction.

AIR insulin capsules of different dose strengths may be combined to yield equivalent pharmacokinetics and glucodynamics.

PubMed

de la Peña, Amparo; Seger, Mary; Rave, Klaus; Heinemann, Lutz; Silverman, Bernard; Muchmore, Douglas B

2009-09-01

In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects. Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5-18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose. Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6-7.8 mg dose range. AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.

Inhaled alpha 1-antitrypsin: gauging patient interest in a new treatment.

PubMed

Monk, Richard; Graves, Michael; Williams, Pamela; Strange, Charlie

2013-08-01

Given the high cost of plasma derived intravenous alpha 1-antitrypsin (AAT), a more efficient method of delivery to the lungs is desirable. Inhaled AAT has been shown feasible for the treatment of alpha 1-antitrypsin deficiency (AATD) and is currently in clinical trials. To better understand patient preferences about possible inhaled AAT therapy, a survey was conducted to explore patient attitudes. We conducted an email based survey of patients in the Alpha-1 Foundation Research Registry with AATD on intravenous AAT replacement. Respondents were asked to rate their interest in hypothetical nebulized or dry powder inhaled AAT. Respondents reported high levels of interest in both dried powder inhaler and nebulizer delivered inhaled AAT. The interest in dried powder inhaled was higher than interest in nebulized AAT (71% vs 64%, p = 0.0001). The interest in dried powder inhaled AAT was particularly high in respondents currently on bronchodilator therapy (p = 0.0053). Patients were just as likely to use or not use the product if it required 20% more out of pocket cost. There is a high level of patient interest in the development of a commercially available inhaled AAT replacement product.

Reliability of Use, Abuse, and Dependence of Four Types of Inhalants in Adolescents and Young Adults

PubMed Central

Ridenour, Ty A.; Bray, Bethany C.; Cottler, Linda B.

2007-01-01

Inhalants, as a class of drugs, consists of heterogeneous substances that include some of the most dangerous drugs on a per use basis. Research on inhalant abuse has lagged behind other drugs partly because of the need for a diagnostic instrument of different types of inhalants. This study was conducted to obtain reliability estimates for the new Substance Abuse Module DSM-IV inhalants diagnoses for four types of inhalants: aerosols, gases, nitrites, and solvents as well as different diagnostic configurations of inhalant use. Participants were 162 community sample adolescents or young adults (mean age = 20.3 years, SD = 2.4). Two-thirds of the sample was male and 83.3% was Caucasian. Kappas and intraclass correlation coefficients were computed to estimate test-retest reliabilities. Results suggested (a) abuse was more common than dependence (34.6% vs. 12.3%), (b) reliabilities of abuse criteria and diagnosis were good to excellent across subtypes, and (c) reliabilities of dependence criteria and diagnoses were poor to good across subtypes. Alternative configurations of DSM-IV criteria that were consistent with previous research on adolescents provided excellent reliabilities across subtypes of inhalants. Moreover, 11.1% of participants experienced inhalants withdrawal. PMID:17576041

Toxicological perspectives of inhaled therapeutics and nanoparticles.

PubMed

Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Optimizing identification and management of COPD patients – reviewing the role of the community pharmacist

PubMed Central

van Boven, Job F. M.; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2016-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self‐management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow‐up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician–pharmacist collaboration. PMID:27510273

Investigating the effects of nitrous oxide sedation on frontal-parietal interactions.

PubMed

Ryu, Ji-Ho; Kim, Pil-Jong; Kim, Hong-Gee; Koo, Yong-Seo; Shin, Teo Jeon

2017-06-09

Although functional connectivity has received considerable attention in the study of consciousness, few studies have investigated functional connectivity limited to the sedated state where consciousness is maintained but impaired. The aim of the present study was to investigate changes in functional connectivity of the parietal-frontal network resulting from nitrous oxide-induced sedation, and to determine the neural correlates of cognitive impairment during consciousness transition states. Electroencephalography was acquired from healthy adult patients who underwent nitrous oxide inhalation to induce cognitive impairment, and was analyzed using Granger causality (GC). Periods of awake, sedation and recovery for GC between frontal and parietal areas in the delta, theta, alpha, beta, gamma and total frequency bands were obtained. The Friedman test with post-hoc analysis was conducted for GC values of each period for comparison. As a sedated state was induced by nitrous oxide inhalation, power in the low frequency band showed increased activity in frontal regions that was reversed with discontinuation of nitrous oxide. Feedback and feedforward connections analyzed in spectral GC were changed differently in accordance with EEG frequency bands in the sedated state by nitrous oxide administration. Calculated spectral GC of the theta, alpha, and beta frequency regions in the parietal-to-frontal direction was significantly decreased in the sedated state while spectral GC in the reverse direction did not show significant change. Frontal-parietal functional connectivity is significantly affected by nitrous oxide inhalation. Significantly decreased parietal-to-frontal interaction may induce a sedated state. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical and functional characteristics of patients two years after being affected by the soybean asthma epidemic in Barcelona.

PubMed Central

Sabrià, J.; Antó, J. M.; Sunyer, J.; Roca, J.; Morell, F.; Rodríguez-Roisín, R.; Rodrigo, M. J.; Codina, R.

1994-01-01

BACKGROUND--Patients affected during the asthma outbreaks caused by soybean dust inhalation in Barcelona presented with sudden onset of severe asthma followed by the rapid relief of symptoms after treatment. Two years after the epidemics ended, a case-control study was conducted in which the clinical, functional, and immunological characteristics of these asthma patients (a randomised sample of asthmatic patients admitted as emergency cases on epidemic days, n = 213) were compared with those of a control group (a random sample of asthmatic patients admitted as emergency cases for attacks of asthma on non-epidemic days, n = 170). METHODS--The study included the administration of the ATS-DLD78 standardised respiratory questionnaire, the measurement of atopy, and performance of spirometric tests and a methacholine inhalation test. RESULTS--Patients with epidemic asthma reported fewer symptoms of asthma, had attended emergency departments less frequently during the previous year for acute attacks of asthma, were taking fewer inhaled corticosteroids at the time of the study, and attended medical follow up less frequently than did the patients with non-epidemic asthma. However, the cases and controls showed no differences in ventilatory capacity or reactivity to the methacholine bronchoprovocation test. CONCLUSIONS--Two years after the end of the soybean epidemics, people affected by epidemic asthma had a favourable prognosis. This finding contrasts with a higher risk of life threatening asthma and death during the epidemics. This paradox could be the result of a complex interaction between host and conditions of exposure. Images PMID:7940432

Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma.

PubMed

Reinero, Carol R; Decile, Kendra C; Byerly, Jenni R; Berghaus, Roy D; Walby, William E; Berghaus, Londa J; Hyde, Dallas M; Schelegle, Edward S; Gershwin, Laurel J

2005-07-01

To compare the effects of an orally administered corticosteroid (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a control substance on the asthmatic phenotype in cats with experimentally induced asthma. 6 cats with asthma experimentally induced by the use of Bermuda grass allergen (BGA). A randomized, crossover design was used to assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA determined by use of ELISAs. Mean +/- SE eosinophil percentages in BALF when cats were administered prednisone (5.0 +/- 2.3%) and flunisolide (2.5 +/- 1.7%) were significantly lower than for the control treatment (33.7 +/- 11.1%). We did not detect significant differences in airway hyperresponsiveness or lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum was significantly lower when cats were treated with prednisone (25.5 +/- 5.4%), compared with values for the control treatment (63.6 +/- 12.9%); no other significant differences were observed in content of BGA-specific immunoglobulins among treatments. Orally administered and inhaled corticosteroids decreased eosinophilic inflammation in airways of cats with experimentally induced asthma. Only oral administration of prednisone decreased the content of BGA-specific IgE in serum; no other significant local or systemic immunologic effects were detected among treatments. Inhaled corticosteroids can be considered as an alternate method for decreasing airway inflammation in cats with asthma.

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

PubMed

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Quick-Relief Medications for Lung Diseases

MedlinePlus

... Rotahaler® Turbuhaler® Twisthaler® Metered-Dose Inhaler (MDI) HFA Propellant Metered-Dose Inhaler and Spacer AeroChamber® AeroChamber® with ... Rotahaler® Turbuhaler® Twisthaler® Metered-Dose Inhaler (MDI) HFA Propellant Metered-Dose Inhaler and Spacer AeroChamber® AeroChamber® with ...

78 FR 70531 - Foreign-Trade Zone (FTZ) 93-Raleigh/Durham, North Carolina; Notification of Proposed Production...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-26

.... The finished products include devices such as respiratory placebo inhalers, Relenza anti-viral inhalers, Seretide/Advair, Serevent and Flovent diskus respiratory inhalers, Advair and Ventolin HFA respiratory inhalers, and the following tablets and capules--Lovaza antihyperlipidemic, Paxil depression...

Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD

PubMed Central

Izquierdo, José Luis; Paredero, José Manuel; Piedra, Raul

2016-01-01

Introduction The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence. Methods We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014. Results During 2013, the medication collected was 7.4%–10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient’s sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014. Conclusion The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence. PMID:26929614

Relevance of dosage in adherence to treatment with long-acting anticholinergics in patients with COPD.

PubMed

Izquierdo, José Luis; Paredero, José Manuel; Piedra, Raul

2016-01-01

The aim of this study was to assess the degree of adherence for two standard regimens for administrating anticholinergic drugs (12 and 24 hours) in patients with chronic obstruction of the airflow and to establish whether the use of a once-daily dose improves the level of treatment adherence. We used long-acting anticholinergics (LAMAs) as a study variable, and included the entire health area of Castile-La Mancha, numbering 2,100,998 inhabitants, as the study population. We analyzed a total of 16,446 patients who had been prescribed a LAMA between January 1, 2013 and December 31, 2013. The follow-up period, based on a centralized system of electronic prescription management, was extended until December 2014. During 2013, the medication collected was 7.4%-10.7% higher than indicated by labeling. This was very similar for all LAMAs, irrespective of the patient's sex, the molecule, the device, and the drug dosage. We did not observe seasonal variations in the consumption of LAMAs, nor did we detect differences between prescription drugs for once-daily (every 24 hours) versus twice-daily (every 12 hours) administration, between the different molecules, or between different types of inhalers for the same molecule. The results were similar in 2014. The principal conclusion of this study is that, in an area with a centralized management system of pharmacological prescriptions, adherence to treatment with LAMAs is very high, irrespective of the molecules or inhalation device. We did not find that patients who used twice-daily medication had a lower adherence.

The relationship between perioperative administration of inhaled corticosteroid and postoperative respiratory complications after pulmonary resection for non-small-cell lung cancer in patients with chronic obstructive pulmonary disease.

PubMed

Yamanashi, Keiji; Marumo, Satoshi; Shoji, Tsuyoshi; Fukui, Takamasa; Sumitomo, Ryota; Otake, Yosuke; Sakuramoto, Minoru; Fukui, Motonari; Huang, Cheng-Long

2015-12-01

Inhaled corticosteroid (ICS) treatment has been shown to increase the risk of respiratory complications in patients with stable chronic obstructive pulmonary disease (COPD). However, the effects of perioperative ICS treatment on postoperative respiratory complications after lung cancer surgery have not been elucidated. The aim of this study was to investigate whether perioperative ICS treatment would increase the risk of postoperative respiratory complications after lung cancer surgery in patients with COPD. We retrospectively analyzed 174 consecutive COPD patients with non-small-cell lung cancer (NSCLC) who underwent lobectomy or segmentectomy between January 2007 and December 2014. Subjects were grouped based on whether or not they were administered perioperative ICS treatment. Postoperative cardiopulmonary complications were compared between the groups. There were no statistically significant differences in the incidence of postoperative respiratory complications (P = 0.573) between the perioperative ICS treatment group (n = 16) and the control group (n = 158). Perioperative ICS treatment was not significantly associated with postoperative respiratory complications in the univariate or multivariate analysis (odds ratio [OR] = 0.553, 95% confidence interval [CI] = 0.069-4.452, P = 0.578; OR = 0.635, 95% CI = 0.065-6.158, P = 0.695, respectively). Kaplan-Meier analysis showed that there were no statistically significant differences in the postoperative respiratory complications-free durations between the groups (P = 0.566), even after propensity score matching (P = 0.551). There was no relationship between perioperative ICS administration and the incidences of postoperative respiratory complications after surgical resection for NSCLC in COPD patients.

Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler.

PubMed

Robertson, C F; Norden, M A; Fitzgerald, D A; Connor, F L; Van Asperen, P P; Cooper, P J; Francis, P W; Allen, H D

1998-04-01

To compare the efficacy of salbutamol delivered by jet nebuliser (JN) with salbutamol via a pressurised metered dose inhaler (PMDI) and a large volume spacer (Volumatic) for management of acute asthma. A total of 160 children aged from 4 to 12 years presenting to an Emergency Department with acute asthma. The study was of multicentre (n=5) randomised, double blind, parallel design. Children weighing less than 25 kg received salbutamol 2.5 mg via the JN or 600 microg (six puffs) from the PMDI. Children over 25 kg received salbutamol 5 mg via the JN or 1200 microg (12 puffs) via the PMDI. Clinical score (range 0-12) and PEF (over 7 years) were recorded at baseline and 15, 30, 45 and 60 mins post administration. The improvement from baseline at 30 min in the clinical score was 1.87 for JN and 1.43 for PMDI (P=0.09) and at 60 min was 2.15 for JN and 1.12 for PMDI (P=0.0001). The improvement in PEF at 30 min was 51 L min(-1) for JN and 27 L min(-1) for PMDI (P=0.0007) and at 60 min was 57 L min(-1) for JN and 31.5 L min(-1) for PMDI (P=0.001). Administration of salbutamol via a PMDI and a large volume spacer device provides effective relief in the management of acute asthma in children, but to a lesser extent than a jet nebuliser. This difference may represent a dose response effect.

Evaluation of simethicone for the treatment of postoperative abdominal discomfort in infants.

PubMed

Voepel-Lewis, T D; Malviya, S; Burke, C; D'Agostino, R; Hadden, S M; Siewert, M; Tait, A R

1998-03-01

To determine whether abdominal discomfort is a cause for distress symptoms in infants following administration of inhalational anesthesia, and to evaluate the effectiveness of simethicone in treating this discomfort. Randomized, double-blinded study. Large tertiary care, university-based medical center. 175 ASA physical status I and II infants under 28 months of age who underwent an inhalational anesthetic for a variety of procedures that were expected to cause relatively little pain. Children were assessed for the presence of postoperative abdominal discomfort, and, if evident, were randomly given either simethicone or placebo in a double-blinded fashion. Abdominal discomfort was measured using the Faces Legs Activity Cry and Consolability (FLACC) Behavioral Pain Scale. Scores were recorded pre-drug; at 10, 20, and 30 minutes following drug administration; and at discharge. If discomfort had not resolved within 15 minutes after the drug was given, routine analgesics or other medications were administered. Abdominal girth was measured preoperatively, on admission into the postanesthesia care unit (PACU), and at discharge. 21% of infants exhibited symptoms of abdominal discomfort postoperatively. Younger infants were at greater risk for this condition. 36 infants were given either placebo or simethicone, and of these, infants who received simethicone were comfortable earlier and required fewer rescue medications compared with placebo. There were no differences in ability to tolerate oral fluids prior to discharge or in the length of stay in the PACU. Simethicone is a safe and inexpensive medication that may provide anesthesiologists with an effective treatment choice for suspected postoperative abdominal discomfort in infants.

[Inductions and intubating conditions with sevoflurane and different doses of remifentanil without muscle relaxant in children].

PubMed

Wei, Ling-Xin; Deng, Xiao-Ming; Liu, Ju-Hui; Luo, Mao-Ping; Tong, Shi-Yi; Zhang, Yan-Ming; Liao, Xu; Xu, Kun-Lin

2008-12-01

To observe the clinical effectiveness of inductions and tracheal intubating conditions with 3% sevoflurane and different doses of remifentanil without muscle relaxant in children. Totally 120 peadiatric patients (aged 4-10 years, American Society of Anesthesiologists grade I for inhalational induction) were randomly allocated into group I (remifentanil 1 microg/kg), group II (remifentanil 2 microg/kg), group III (remifentanil 3 microg/kg), and control group (vecuronium bromide 0.1 mg/kg). After inhalational induction with 3% sevoflurane and 60% nitrous oxide in 40% oxygen for 2 minutes, remifentanil 1 microg/kg, 2 microg/ kg, and 3 microg/kg were intravenously injected over 1 minute into patients in group I , group II, and group III, respectively. After remifentanil administration and manual ventilation for 1 minute, the trachea was intubated. In the control group, 2 minutes after intravenous administration of vecuronium bromide 0.1 mg/kg, tracheal intubation was attempted. Agitation, intubating satisfactoriness, and the circulation changes after tracheal intubation and anesthesia induction were observed. In these four groups, agitation occurred in 37.5% of patients during sevoflurane induction. Satisfactory intubation rate was 70.0% in group I, 86.7% in group II, 90.0% in group III, and 93.3% in the control group. Compared with the control group, the impact of tracheal intubation on the circulatory system was smaller in group I , II , and III. Induction with 3% sevoflurane combined with remifentanil can be smoothly performed, followed by the successful tracheal intubation. The intubating conditions are more satisfactory with 3% sevoflurane combined with remifentanil 2 microg/kg or 3 microg/kg.

Advances in Audio-Based Systems to Monitor Patient Adherence and Inhaler Drug Delivery.

PubMed

Taylor, Terence E; Zigel, Yaniv; De Looze, Céline; Sulaiman, Imran; Costello, Richard W; Reilly, Richard B

2018-03-01

Hundreds of millions of people worldwide have asthma and COPD. Current medications to control these chronic respiratory diseases can be administered using inhaler devices, such as the pressurized metered dose inhaler and the dry powder inhaler. Provided that they are used as prescribed, inhalers can improve patient clinical outcomes and quality of life. Poor patient inhaler adherence (both time of use and user technique) is, however, a major clinical concern and is associated with poor disease control, increased hospital admissions, and increased mortality rates, particularly in low- and middle-income countries. There are currently limited methods available to health-care professionals to objectively and remotely monitor patient inhaler adherence. This review describes recent sensor-based technologies that use audio-based approaches that show promising opportunities for monitoring inhaler adherence in clinical practice. This review discusses how one form of sensor-based technology, audio-based monitoring systems, can provide clinically pertinent information regarding patient inhaler use over the course of treatment. Audio-based monitoring can provide health-care professionals with quantitative measurements of the drug delivery of inhalers, signifying a clear clinical advantage over other methods of assessment. Furthermore, objective audio-based adherence measures can improve the predictability of patient outcomes to treatment compared with current standard methods of adherence assessment used in clinical practice. Objective feedback on patient inhaler adherence can be used to personalize treatment to the patient, which may enhance precision medicine in the treatment of chronic respiratory diseases. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The importance of continuity in inhaler device choice for asthma and chronic obstructive pulmonary disease.

PubMed

Bjermer, Leif

2014-01-01

Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease. Physicians consider many factors when selecting the most appropriate inhaler device, including device efficacy and the cost to the health care system. This review aims to discuss the factors that are important when considering inhaler devices and the importance of continuity in the choice of inhaler device. A large number of factors can contribute to therapeutic outcomes with inhalation devices. The inhalation technique is critical to treatment success and differs substantially between inhaler devices. Misuse of an inhaler is common, and thorough training of patients and physicians is important to ensure correct utilization. Patient satisfaction is an important consideration because it is significantly correlated with compliance and better outcomes. Financial pressures contribute to decision making: although selecting the less expensive inhaler device might reduce direct treatment costs, it can have a large impact on disease control and the patient's well-being. Switching may be associated with a poor inhalation technique, reduced disease control and quality of life, increased use of other treatments and health care resources, and a greater chance of unsuccessful treatment. Nonconsensual switches can result in patient discontent, reduced confidence in the medication, and uncertainty regarding the degree of disease control. It is recommended that patients with stable disease remain on their current device. If a switch is considered, the patient should be consulted and the physician should take into account the patient's preference, their ability to correctly use the device, and the availability of the preferred drug in the preferred device.

Inhalant use among schoolchildren in northeast India: a preliminary study.

PubMed

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

2013-01-01

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

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. © 2014 Society for Risk Analysis.

Physical Symptoms and Psychological Distress among Inhalant Users.

ERIC Educational Resources Information Center

Joe, George W.; And Others

1991-01-01

Among 110 Mexican-American adolescents with varying drug use histories, self-reported physical health problems were not related to inhalant use history, but blood analyses indicated a relationship between extensive inhalant use and liver problems. Psychological distress symptoms were related to inhalant use and physical symptoms. Contains 23…

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

Intermittent Oxygen Inhalation with Proper Frequency Improves Overall Health Conditions and Alleviates Symptoms in a Population at High Risk of Chronic Mountain Sickness with Severe Symptoms

PubMed Central

Feng, Bin; Xu, Wei-Hao; Gao, Yu-Qi; Liu, Fu-Yu; Li, Peng; Zheng, Shan-Jun; Gai, Lu-Yue; Zhang, Gang

2016-01-01

Background: Oxygen inhalation therapy is essential for the treatment of patients with chronic mountain sickness (CMS), but the efficacy of oxygen inhalation for populations at high risk of CMS remains unknown. This research investigated whether oxygen inhalation therapy benefits populations at high risk of CMS. Methods: A total of 296 local residents living at an altitude of 3658 m were included; of which these were 25 diagnosed cases of CMS, 8 cases dropped out of the study, and 263 cases were included in the analysis. The subjects were divided into high-risk (180 ≤ hemoglobin (Hb) <210 g/L, n = 161) and low-risk (Hb <180 g/L, n = 102) groups, and the cases in each group were divided into severe symptom (CMS score ≥6) and mild symptom (CMS score 0-5) subgroups. Severe symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group) or oxygen intake 7 times/week group (D group); mild symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group), oxygen intake 2 times/week group (B group), and 4 times/week group (C group). The courses for oxygen intake were all 30 days. The CMS symptoms, sleep quality, physiological biomarkers, biochemical markers, etc., were recorded on the day before oxygen intake, on the 15th and 30th days of oxygen intake, and on the 15th day after terminating oxygen intake therapy. Results: A total of 263 residents were finally included in the analysis. Among these high-altitude residents, CMS symptom scores decreased for oxygen inhalation methods B, C, and D at 15 and 30 days after oxygen intake and 15 days after termination, including dyspnea, palpitation, and headache index, compared to those before oxygen intake (B group: Z = 5.604, 5.092, 5.741; C group: Z = 4.155, 4.068, 4.809; D group: Z = 6.021, 6.196, 5.331, at the 3 time points respectively; all P < 0.05/3 vs. before intake). However, dyspnea/palpitation (A group: Z = 5.003, 5.428, 5.493, both P < 0.05/3 vs. before intake) and headache (A group: Z = 4.263, 3.890, 4.040, both P < 0.05/3 vs. before intake) index decreased significantly also for oxygen inhalation method A at all the 3 time points. Cyanosis index decreased significantly 30 days after oxygen intake only in the group of participants administered the D method (Z = 2.701, P = 0.007). Tinnitus index decreased significantly in group A and D at 15 days (A group: Z = 3.377, P = 0.001, D group: Z = 3.150, P = 0.002), 30 days after oxygen intake (A group: Z = 2.836, P = 0.005, D group: Z = 5.963, P < 0.0001) and 15 days after termination (A group: Z = 2.734, P = 0.006, D group: Z = 4.049, P = 0.0001), and decreased significantly in the group B and C at 15 days after termination (B group: Z = 2.611, P = 0.009; C group: Z = 3.302, P = 0.001). In the population at high risk of CMS with severe symptoms, oxygen intake 7 times/week significantly improved total symptom scores of severe symptoms at 15 days (4 [2, 5] vs. 5.5 [4, 7], Z = 2.890, P = 0.005) and 30 days (3 [1, 5] vs. 5.5 [2, 7], Z = 3.270, P = 0.001) after oxygen intake compared to no oxygen intake. In the population at high risk of CMS with mild symptoms, compared to no oxygen intake, oxygen intake 2 or 4 times/week did not improve the total symptom scores at 15 days (2 [1, 3], 3 [1, 4] vs. 3 [1.5, 5]; χ2= 2.490, P = 0.288), and at 30 days (2 [0, 4], 2 [1, 4.5] vs. 3 [2, 5]; χ2= 3.730, P = 0.155) after oxygen intake. In the population at low risk of CMS, oxygen intake did not significantly change the white cell count and red cell count compared to no oxygen intake, neither in the severe symptomatic population nor in the mild symptomatic population. Conclusions: Intermittent oxygen inhalation with proper frequency might alleviate symptoms in residents at high altitude by improving their overall health conditions. Administration of oxygen inhalation therapy 2–4 times/week might not benefit populations at high risk of CMS with mild CMS symptoms while administration of therapy 7 times/week might benefit those with severe symptoms. Oxygen inhalation therapy is not recommended for low-risk CMS populations. PMID:27231170

COPD - control drugs

MedlinePlus

Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - ...

Inhalation delivery of protein therapeutics.

PubMed

Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

2013-04-01

Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

Focus on Inhalants.

ERIC Educational Resources Information Center

Challenge: Safe, Disciplines, and Drug-Free Schools, 1994

1994-01-01

The use of inhalants is a major health concern among the school-age population. Information presented in this publication dispels the myths about inhalant use and presents common warning signs that alert teachers to a student's use. The short- and long-term effects of inhalant use are described to shed light on the health risks involved. Lesson…

STATUS REPORT: EVIDENCE BASED ADVANCES IN INHALATION DOSIMETRY FOR GASES WITH EFFECTS IN THE LOWER RESPIRATORY TRACT AND IN THE BODY

EPA Science Inventory

This report summarizes the status of specific inhalation dosimetry procedures for gases as outlined in U.S. EPA’s 1994 Methods for Derivation of Inhalation Reference Concentrations and Applications of Inhalation Dosimetry (U.S. EPA 1994) and reviews recent scientific advances in...

Hydrazine inhalation hepatotoxicity.

PubMed

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

2007-10-01

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

49 CFR 172.429 - POISON INHALATION HAZARD label.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

49 CFR 172.429 - POISON INHALATION HAZARD label.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

49 CFR 172.429 - POISON INHALATION HAZARD label.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

49 CFR 172.555 - POISON INHALATION HAZARD placard.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

49 CFR 172.429 - POISON INHALATION HAZARD label.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

49 CFR 172.429 - POISON INHALATION HAZARD label.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

Hydrodynamics of Low Reynolds Respiratory-type Flows

NASA Astrophysics Data System (ADS)

Connor, Erin; True, Aaron; Crimaldi, John

2017-11-01

Both aquatic and terrestrial animals inhale surrounding fluid for metabolic and sensory purposes. As organisms inhale and exhale, complex fluid interactions occur both internal and external to the physiological orifice. Using both numerical and experimental approaches, we model an idealized respiratory flow consisting of cyclic inhalation and exhalation through a single cylindrical tube. We investigate the effect of varying Reynolds number (Re) as well as the ratio of the inhalation time to the exhalation time (I:E ratio) for a fixed inhalation volume. The numerical model is used for laminar cases at lower Re, whereas the experimental model permits the study to be extended into higher Reynolds numbers that include transitions to turbulence. We map the spatial distribution of both inhaled and exhaled fluid volumes. By comparing these two maps, we can compute the volume of exhaled fluid that is reingested during the subsequent inhalation. The models of interacting inhalation and exhalation exhibit a rich range of flow behaviors across Re number and I:E ratio. This study builds a foundation for more complex studies of animal respiration that will include more realistic morphologies.

Inhaler use in adolescents and adults with self-reported physician-diagnosed asthma, bronchitis, or emphysema in the city of Pelotas, Brazil*

PubMed Central

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

2013-01-01

OBJECTIVE: To evaluate the characteristics of users of inhalers and the prevalence of inhaler use among adolescents and adults with self-reported physician-diagnosed asthma, bronchitis, or emphysema. METHODS: A population-based study conducted in the city of Pelotas, Brazil, involving 3,670 subjects ≥ 10 years of age, evaluated with a questionnaire. RESULTS: Approximately 10% of the sample reported at least one of the respiratory diseases studied. Among those individuals, 59% reported respiratory symptoms in the last year, and, of those, only half reported using inhalers. The use of inhalers differed significantly by socioeconomic status (39% and 61% for the lowest and the highest, respectively, p = 0.01). The frequency of inhaler use did not differ by gender or age. Among the individuals reporting emphysema and inhaler use, the use of the bronchodilator-corticosteroid combination was more common than was that of a bronchodilator alone. Only among the individuals reporting physician-diagnosed asthma and current symptoms was the proportion of inhaler users higher than 50%. CONCLUSIONS: In our sample, inhalers were underutilized, and the type of medication used by the individuals who reported emphysema does not seem to be in accordance with the consensus recommendations. PMID:23857689

Anxiety symptoms in crack cocaine and inhalant users admitted to a psychiatric hospital in southern Brazil.

PubMed

Zubaran, Carlos; Foresti, Katia; Thorell, Mariana Rossi; Franceschini, Paulo Roberto

2013-01-01

The occurrence of psychiatric comorbidity among individuals with crack or inhalant dependence is frequently observed. The objective of this study was to investigate anxiety symptoms among crack cocaine and inhalant users in southern Brazil. The study investigated two groups of volunteers of equal size (n=50): one group consisted of crack cocaine users, and the other group consisted of inhalant users. Research volunteers completed the Portuguese versions of the State-Trait Anxiety Inventory (STAI), Hamilton Anxiety Rating Scale (HAM-A), and Self-Report Questionnaire (SRQ). Both crack and inhalant users experience significant symptoms of anxiety. Inhalant users presented significantly more anxiety symptoms than crack users according to the HAM-A questionnaire only. In contrast to the results of the HAM-A, the STAI failed to demonstrate a significant difference between the two groups of substance users. SRQ scores revealed that crack and inhalants users had significant degrees of morbidity. A significant difference regarding anxiety symptomatology, especially state anxiety, was observed among inhalant and crack users. Anxiety and overall mental psychopathology were significantly correlated in this sample. The results indicate that screening initiatives to detect anxiety and additional psychiatric comorbidities among crack and inhalant users are feasible and relevant. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Introduction of Inhaled Nitrous Oxide and Oxygen for Pain Management during Labour – Evaluation of Patientsʼ and Midwivesʼ Satisfaction

PubMed Central

Dammer, U.; Weiss, C.; Raabe, E.; Heimrich, J.; Koch, M. C.; Winkler, M.; Faschingbauer, F.; Beckmann, M. W.; Kehl, S.

2014-01-01

Aim: Effective pain management during labour is important because pain affects the birth experience. Epidural analgesia is effective but often it may not be possible; however, inhaled analgesia offers another option. Use of inhaled nitrous oxide and oxygen for pain management in labour is well established in obstetrics but is still not used much in Germany. This study aimed to investigate the acceptance of the inhaled analgesia of inhaled nitrous oxide and oxygen by midwives and pregnant women during labour. Material and Methods: In this observational study carried out between April and September 2013, a total of 66 pregnant women received inhaled nitrous oxide and oxygen during labour on request and after prior assessment of suitability. After the birth, all of the women and the responsible midwives were interviewed about their experience and satisfaction with the inhaled analgesia. Results: A statistically significant reduction of pain was achieved with nitrous oxide and oxygen. The inhaled analgesia was mostly used by women who refused epidural analgesia. The likelihood of using inhaled nitrous oxide and oxygen again was reported as higher for patients who tolerated it well (p = 0.0129) and used it in the second stage of labour (p = 0.0003) and when bearing down (p = 0.0008). Conclusion: Inhaled nitrous oxide and oxygen is an effective method for pain management during labour and is accepted well by women in labour and by midwives. PMID:25100880

Age-related differences in recovery from inhalational anesthesia: a retrospective study.

PubMed

Tsukamoto, Masanori; Yamanaka, Hitoshi; Yokoyama, Takeshi

2018-03-03

It is important to understand the anesthetic requirements of elderly patients. However, little is known about age-related recovery from inhalational anesthetics. In this retrospective study, we compared age-related differences in recovery from three inhalational anesthetics  in elderly subjects. Patients were investigated as three age groups which can be defined as age ranges pediatric (< 15 years), adult (15-64 years), and elderly patients ( > 65 years) under general anesthesia using inhalational anesthetics. Anesthesia and surgery times, drug end-tidal concentrations, the time to first movement, time to eye opening, body movement, extubation, and discharge were recorded. The data were analyzed using a Kruskal-Wallis test and Steel-Dwass multiple comparisons. A total of 594 patients were included in the study. In inhalational anesthetics such as sevoflurane, isoflurane, or desflurane, recovery from general anesthesia was not significantly different among age groups (P > 0.05). In inhalational group, recovery was significantly 5-40% faster in desflurane group than in other inhalational anesthetics groups (P < 0.05). There were 20% faster recovery in pediatric and adult groups with desflurane than in elderly with desflurane group. Drug end-tidal inhalational concentrations in pediatric group were significantly higher than that in adult and elderly groups of all inhalational anesthetics, respectively (P < 0.05). In the current study, we have found that recovery from desflurane was faster in younger patients than in other inhalational anesthetics and aged patients.

Economic considerations in the use of inhaled anesthetic agents.

PubMed

Golembiewski, Julie

2010-04-15

To describe the components of and factors contributing to the costs of inhaled anesthesia, basis for quantifying and comparing these costs, and practical strategies for performing pharmacoeconomic analyses and reducing the costs of inhaled anesthetic agents. Inhaled anesthesia can be costly, and some of the variable costs, including fresh gas flow rates and vaporizer settings, are potential targets for cost savings. The use of a low fresh gas flow rate maximizes rebreathing of exhaled anesthetic gas and is less costly than a high flow rate, but it provides less control of the level of anesthesia. The minimum alveolar concentration (MAC) hour is a measure that can be used to compare the cost of inhaled anesthetic agents at various fresh gas flow rates. Anesthesia records provide a sense of patterns of inhaled anesthetic agent use, but the amount of detail can be limited. Cost savings have resulted from efforts to reduce the direct costs of inhaled anesthetic agents, but reductions in indirect costs through shortened times to patient recovery and discharge following the judicious use of these agents are more difficult to demonstrate. The patient case mix, fresh gas flow rates typically used during inhaled anesthesia, availability and location of vaporizers, and anesthesia care provider preferences and practices should be taken into consideration in pharmacoeconomic evaluations and recommendations for controlling the costs of inhaled anesthesia. Understanding factors that contribute to the costs of inhaled anesthesia and considering those factors in pharmacoeconomic analyses and recommendations for use of these agents can result in cost savings.

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

PubMed Central

Westerik, Janine A. M.; Carter, Victoria; Chrystyn, Henry; Burden, Anne; Thompson, Samantha L.; Ryan, Dermot; Gruffydd-Jones, Kevin; Haughney, John; Roche, Nicolas; Lavorini, Federico; Papi, Alberto; Infantino, Antonio; Roman-Rodriguez, Miguel; Bosnic-Anticevich, Sinthia; Lisspers, Karin; Ställberg, Björn; Henrichsen, Svein Høegh; van der Molen, Thys; Hutton, Catherine; Price, David B.

2016-01-01

Abstract Objective: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). Methods: This was a historical, multinational, cross-sectional study (2011–2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. Results: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26–3.40); obesity (OR 1.75; 1.17–2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04–2.36); female sex (OR 1.51; 1.08–2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04–2.02). Conclusions: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID:26810934

Inhaler technique maintenance: gaining an understanding from the patient's perspective.

PubMed

Ovchinikova, Ludmila; Smith, Lorraine; Bosnic-Anticevich, Sinthia

2011-08-01

The aim of this study was to determine the patient-, education-, and device-related factors that predict inhaler technique maintenance. Thirty-one community pharmacists were trained to deliver inhaler technique education to people with asthma. Pharmacists evaluated (based on published checklists), and where appropriate, delivered inhaler technique education to patients (participants) in the community pharmacy at baseline (Visit 1) and 1 month later (Visit 2). Data were collected on participant demographics, asthma history, current asthma control, history of inhaler technique education, and a range of psychosocial aspects of disease management (including adherence to medication, motivation for correct technique, beliefs regarding the importance of maintaining correct technique, and necessity and concern beliefs regarding preventer therapy). Stepwise backward logistic regression was used to identify the predictors of inhaler technique maintenance at 1 month. In total 145 and 127 participants completed Visits 1 and 2, respectively. At baseline, 17% of patients (n = 24) demonstrated correct technique (score 11/11) which increased to 100% (n = 139) after remedial education by pharmacists. At follow-up, 61% (n = 77) of patients demonstrated correct technique. The predictors of inhaler technique maintenance based on the logistic regression model (X(2) (3, N = 125) = 16.22, p = .001) were use of a dry powder inhaler over a pressurized metered-dose inhaler (OR 2.6), having better asthma control at baseline (OR 2.3), and being more motivated to practice correct inhaler technique (OR 1.2). Contrary to what is typically recommended in previous research, correct inhaler technique maintenance may involve more than repetition of instructions. This study found that past technique education factors had no bearing on technique maintenance, whereas patient psychosocial factors (motivation) did.

Parameters affecting inhalation therapy adherence in elderly patients with chronic obstructive lung disease and asthma.

PubMed

Turan, Onur; Turan, Pakize Ayse; Mirici, Arzu

2017-06-01

One of the most significant problems in the treatment of elderly patients is incorrect use of inhaler devices. The purpose of the present study was to assess the parameters affecting treatment adherence among elderly patients. Spirometry, the Mini-Mental State Examination for cognitive impairment and the Morisky Medication Adherence Scale-4 were carried out in 121 (88 chronic obstructive lung disease patients according to the Global Initiative for Chronic Obstructive Lung Disease, 33 asthma patients according to The Global Initiative for Asthma (GINA) criteria) participants aged over 65 years. The patients with cognitive impairment, low socioeconomic status, a high number of admissions to an emergency service in past year and the presence of dyspnea or sputum had significantly lower inhalation device use scores (P = 0.017, 0.03, 0.025, 0.03 and 0.02). The patients with high Mini-Mental State Examination scores and forced expiratory volume in 1 s (as liter and percentage) were found to be more successful in using inhaler devices (P = 0.005, 0.007 and 0.022). There was a negative correlation between number of hospitalizations and inhalation device score (P = 0.021).The participants without education/training by a doctor about the inhaler device had a significantly poorer treatment adherence (P < 0.001). Older chronic obstructive lung disease and asthmatic patients have more difficulty with the correct use of inhaler devices. Cognitive impairment might be an important parameter that can affect inhalation device technique. Socioeconomic status, smoking, pulmonary symptoms and admissions to hospital were also thought to have effects on the adherence to inhalation therapy. The type of chronic respiratory disease (chronic obstructive lung disease/asthma) is not a major factor influencing therapy adherence. Assessment of cognitive functions, choosing suitable inhalation devices and educational programs for inhaler use could improve the success of inhaler technique in elderly patients. Geriatr Gerontol Int 2017; 17: 999-1005. © 2016 Japan Geriatrics Society.

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

PubMed

Gigengack, Roy

2014-07-01

Inhalant use has existed in India since the 1970s and has increased significantly over the last decades, especially among street-oriented young people. The latter constitute a heterogeneous category: children from street families, children 'of' the street, rag pickers, and part-time street children. There are also inhalant-using schoolchildren and young people in slums. Fieldwork was conducted for 1 year. Team ethnography, multi-sited and comparative research, flexibility of methods and writing field notes were explicit parts of the research design. Most research was undertaken with six groups in four areas of Delhi, exemplifying six generic categories of inhalant-using street-oriented young people. Inhalants in India are branded: Eraz-Ex diluter and whitener, manufactured by Kores, are used throughout Delhi; Omni glue in one specific area. There is a general lack of awareness and societal indifference towards inhalant use, with the exception of the inhalant users themselves, who possess practical knowledge. They conceive of inhalants as nasha, encapsulating the materiality of the substances and the experiential aspects of intoxication and addiction. Fragments of group interviews narrate the sensory appeal of inhalants, and an ethnographic vignette the dynamics of a sniffing session. These inhalant-using street children seek intoxication in a pursuit of pleasure, despite the harm that befalls them as a result. Some find nasha beautiful, notwithstanding the stigmatization, violence and bodily deterioration; others experience it as an overpowering force. A source of attraction and pleasure, inhalants ravage street children's lives. In this mysterious space of lived experience, their self-organization evolves. Distinguishing between hedonic and side effects, addiction helps to understand inhalant use as at once neurobiological, cultural, and involving agency. The implications are that India needs to develop a policy of treatment and employment to deal with the addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

Is the ‘blue’ colour convention for inhaled reliever medications important? A UK-based survey of healthcare professionals and patients with airways disease

PubMed Central

Fletcher, Monica; Scullion, Jane; White, John; Thompson, Bronwen; Capstick, Toby

2016-01-01

In many countries, short-acting β2-agonist inhalers have traditionally been coloured blue. This inhaled therapy has also conventionally been known as a ‘reliever’ by patients and healthcare professionals (HCPs), in comparison with ‘preventer’ medications (inhaled steroids). With the rapidly changing market in inhaled therapy for COPD and asthma and growing numbers of devices, there has been some concern that the erosion of traditional colour conventions is leading to patients (and HCPs) becoming confused about the role of different therapies. In order to assess whether there was concern over the perceived changing colour conventions, the UK Inhaler Group carried out a large online survey of patients and HCPs. The aim was to determine how patients and HCPS identify and describe inhaled drugs, and how this might impact on use of medicines and safety. The results of the survey highlighted the importance of the term ‘blue inhaler’ for patients with only 11.3% never referring to the colour when referring to their inhaler. For HCPs, 95% felt colour conventions were important when referring to reliever medication. In addition, HCPs appear to refer to inhalers mainly by colour when talking to patients. Our conclusions were that the concept of a ‘blue inhaler’ remains important to patients and healthcare professionals. These results add to the debate about the need to formalise the colour coding of inhaled therapies, in particular using the colour blue for inhalers for rapid relief of symptoms, as this convention may be an important measure and contributor to patient safety. Our survey should provide impetus for all interested parties to discuss and agree a formal industry-wide approach to colour coding of inhaled therapies for the benefit of patients and carers and HCPs. PMID:27808097

Inhalant Use and Delinquent Behaviors among Young Adolescents. The NSDUH Report

ERIC Educational Resources Information Center

US Department of Health and Human Services, 2005

2005-01-01

This report presents the prevalence of inhalant use among young adolescents aged 12 or 13, the association between inhalant use and delinquent behaviors within this age group, and the association between early onset of inhalant use and problems later in life. Early onset of substance use has been linked to substance use disorders, delinquent…

Inhalant Initiation and the Relationship of Inhalant Use to the Use of Other Substances

ERIC Educational Resources Information Center

Shamblen, Stephen R.; Miller, Ted

2012-01-01

Conventional wisdom suggests that inhalant use is primarily isolated to youthful experimentation; however, a growing body of evidence suggests that inhalant use (a) occurs after use of common substances of experimentation (e.g., alcohol, marijuana), (b) can persist into later life, and (c) is associated with severe consequences. The current study…

[Case report - a dangerous intoxication after ingestion of alkyl nitrite ("poppers")].

PubMed

Bernasconi, Barbara; Konrad, Christoph; Fischer, Simon

2014-12-01

This case report describes the inadvertent poisoning of a young man with "poppers" after having ingested an unknown amout of the drug. "Poppers" (alkyl nitrite) were made famous in the 1960s as a party drug, and during certain sexual practices, and are still in use today. The drug's inhalation leads to a short-lived rush, vasodilation and relaxtion of smooth muscles. An accidental ingestion can lead to a significant build-up of methemoglobin with dire consequences. The therapy consists of the intravenous administration of methylene blue. © Georg Thieme Verlag Stuttgart · New York.

Assessing health risks of synthetic vitreous fibers: an integrative approach.

PubMed

McClellan, R O

1994-12-01

This paper reviews a tiered approach to acquiring information from multiple experimental systems to understand and assess the potential human health risks of exposure to airborne synthetic fibers. The approach is grounded in the now widely accepted research-risk assessment-risk management paradigm. It involves the acquisition of information that will provide mechanistic linkages within the exposure-dose-response paradigm. It advocates the use of the inhalation route of exposure for developing relevant information for assessing human health risks and calls attention to serious problems encountered using nonphysiologic routes of administration to assess human health risks.

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.

Protective effect of inhalation of hydrogen gas on radiation-induced dermatitis and skin injury in rats

PubMed Central

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

2014-01-01

The effect of inhalation of hydrogen-containing gas (1.3% hydrogen + 20.8% oxygen + 77.9% nitrogen) (HCG) on radiation-induced dermatitis and on the healing of healing-impaired skin wounds in rats was examined using a rat model of radiation-induced skin injury. An X-ray dose of 20 Gy was irradiated onto the lower part of the back through two holes in a lead shield. Irradiation was performed before or after inhalation of HCG for 2 h. Inhalation of HCG significantly reduced the severity of radiodermatitis and accelerated healing-impaired wound repair. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) showed that the proportion of apoptotic keratinocytes and the level of staining in the X-irradiated skin of rats that pre-inhaled HCG were significantly lower than that of rats which did not pre-inhale HCG. Cutaneous full-thickness wounds were then created in the X-irradiated area to examine the time-course of wound healing. X-irradiation significantly increased the time required for wound healing, but the inhalation of HCG prior to the irradiation significantly decreased the delay in wound healing compared with the control and post-inhalation of HCG groups. Therefore, radiation-induced skin injury can potentially be alleviated by the pre-inhalation of HCG. PMID:25034733

Inhalants

MedlinePlus

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Effects of Chronic Solvent Abuse on Public School Youth.

ERIC Educational Resources Information Center

Fullwood, Harry L.; Fournet, Glenn P.

School youth have been increasingly involved in the dangerous abuse of volatile inhalants. The basic reason to inhale substances is to reach an altered state of consciousness. The 12-17 and 18-25-year-old age groups had the highest rates of inhalant abuse in 1993. Among eighth graders, almost one in five (19%) said they have used inhalants and 5%…

Dynamics of airflow in a short inhalation

PubMed Central

Bates, A. J.; Doorly, D. J.; Cetto, R.; Calmet, H.; Gambaruto, A. M.; Tolley, N. S.; Houzeaux, G.; Schroter, R. C.

2015-01-01

During a rapid inhalation, such as a sniff, the flow in the airways accelerates and decays quickly. The consequences for flow development and convective transport of an inhaled gas were investigated in a subject geometry extending from the nose to the bronchi. The progress of flow transition and the advance of an inhaled non-absorbed gas were determined using highly resolved simulations of a sniff 0.5 s long, 1 l s−1 peak flow, 364 ml inhaled volume. In the nose, the distribution of airflow evolved through three phases: (i) an initial transient of about 50 ms, roughly the filling time for a nasal volume, (ii) quasi-equilibrium over the majority of the inhalation, and (iii) a terminating phase. Flow transition commenced in the supraglottic region within 20 ms, resulting in large-amplitude fluctuations persisting throughout the inhalation; in the nose, fluctuations that arose nearer peak flow were of much reduced intensity and diminished in the flow decay phase. Measures of gas concentration showed non-uniform build-up and wash-out of the inhaled gas in the nose. At the carina, the form of the temporal concentration profile reflected both shear dispersion and airway filling defects owing to recirculation regions. PMID:25551147

Evaluation of Bioequivalence Between the New Procaterol Hydrochloride Hydrate Dry Powder Inhaler and the Approved Dry Powder Inhaler in Patients With Asthma in a Randomized, Double-Blind, Double-Dummy, Crossover Comparison Study: A Phase 3 Study.

PubMed

Shirai, Ryo; Suzaki, Yuki; Sato, Kyoko; Takeuchi, Yuko; Tokimatsu, Issei; Koga, Nobuyuki; Kadota, Junichi; Ohashi, Kyoichi

2018-05-01

Procaterol hydrochloride hydrate (procaterol) is a β 2 -adrenergic receptor agonist that induces a strong bronchodilatory effect. The procaterol dry powder inhaler (DPI) has been frequently used in patients with bronchial asthma or chronic obstructive pulmonary disease. We evaluated the bioequivalence and safety between the new procaterol DPI (new DPI) and the approved procaterol DPI (approved DPI). This study was a randomized, double-blind, double-dummy, crossover comparison to evaluate the pharmacodynamic equivalence of the new DPI and the approved DPI in patients with bronchial asthma. Primary efficacy variables were area under the concentration-time curve (AUC) forced expiratory volume in the first second (FEV 1 )/h and maximum FEV 1 during the 480-minute measurement period. Patients were divided into 2 groups, New-DPI-First (n = 8) and Approved-DPI-First (n = 8), according to the investigational medical product that was administered first. Patients inhaled 20 μg of procaterol in each period. FEV 1 was measured by a spirometer at predose and at 15, 30, 60, 90, 120, 180, 240, 360, and 480 minutes after each investigational medical product administration. Equivalence was evaluated by confirming that the 2-sided 90%CIs for the difference between the new and the approved DPI in means of AUC (FEV 1 )/h and maximum FEV 1 were within the acceptance criteria of -0.15 to 0.15 L. The difference in means of AUC (FEV 1 )/h and maximum FEV 1 was 0.041 L and 0.033 L, respectively, and the 90%CI was 0.004 to 0.078 L and -0.008 to 0.074 L, respectively. These CIs were both within the acceptance criteria. The new DPI was assessed as being bioequivalent to the approved DPI. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Is aclidinium alone or combined with a LABA a rational choice for symptomatic COPD patients?

PubMed

Blasi, F; Canonica, G W; Miravitlles, M

2017-01-18

As emphasized by international recommendations and largely confirmed by clinical experience, long-acting bronchodilators play a central role in the maintenance treatment of chronic obstructive pulmonary disease (COPD) due to their proven efficacy in reducing airflow obstruction and improving symptoms. There are some important aspects to define with regard to inhalation therapy for COPD, particularly those concerning the selection criteria and the optimal use of long-acting bronchodilators. First of all, it needs to be determined in which patients and clinical situations monotherapy with one bronchodilator, such as a long-acting muscarinic antagonist (LAMA), should be considered adequate, and in which cases the use of combination therapies, such as the "double bronchodilation" with a LAMA and a long-acting β2-agonist (LABA), should be preferred. Another critical issue concerns the effect of the frequency of daily administration of inhaled agents on the control of symptoms during the 24 h. COPD symptoms are known to exhibit considerable circadian variability with worsening in the early morning, and a significant proportion of patients have disease-related sleep disorders which can adversely affect their quality of life. The worsening of symptoms in the early morning may be due, at least in part, to a reduction in airway caliber caused by an increased "cholinergic tone" at night. As such, the coverage of nighttime and early morning symptoms is a reasonable therapeutic goal, which can be achieved by many patients using LAMAs such as aclidinium bromide twice daily (BID). Therapeutic adherence is known to be a multifactorial phenomenon that is frequently affected by other aspects than dosing frequency, including the technical features and ease of use of the inhalers. To this end, it should be mentioned that certain new-generation inhalers such as Genuair® have been associated in clinical trials with higher patient preference. In this work, in addition to presenting an overview of the main evidence on the efficacy of COPD treatment with the LAMA aclidinium bromide BID, we suggest some selection criteria for the monotherapy with one long-acting bronchodilator or the combination therapy with LAMA and LABA in COPD patients, with particular reference to specific clinical scenarios.

Formulation of a novel fixed dose combination of salmeterol xinafoate and mometasone furoate for inhaled drug delivery.

PubMed

Liu, Sha; Watts, Alan B; Du, Ju; Bui, Amanda; Hengsawas, Soraya; Peters, Jay I; Williams, Robert O

2015-10-01

Co-administration of an inhaled corticosteroid and long acting beta agonist for chronic obstructive pulmonary disease has reduced mortality compared to either drug alone. This combination reduces exacerbations, hospitalization, emergency department visits and health care costs. A novel fixed-dose combination of the long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid mometasone furoate (MF) were prepared in a composite particle formulation as brittle matrix powder (BMP) and investigated for suitability as an inhaled combination product. In this study, BMP fixed dose combinations of SX and MF with or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were prepared and characterized with respect to their thermal properties, morphology, aerodynamic performance and physical stability. BMP combination formulations of SX and MF exhibited improved aerodynamic properties when delivered by dry powder inhalation as compared to the micronized blends of the same substances. Aerodynamic evaluation was carried out by next generation pharmaceutical impactor (NGI) with a marketed DPI device. Results demonstrated that co-deposition occurred when SX and MF were formulated together as composite particles in a BMP, while physical blends resulted in inconsistent deposition and dose uniformity. As a result of the bottom-up particle engineering approach, combination BMP formulations allow for dual API composite formulations to be dispersed as aerosolized particles. Aerosolized BMP combination formulations resulted in delivered dose uniformity and co-deposition of each API. Further, an excipient-free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the respirable range and demonstrated stability at ambient conditions for 6months. Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue deposition and blood circulation (AUC0-24h) of two APIs were higher for the BMP combination group exhibiting a significantly higher lung concentration of drugs than for the crystalline physical blend. While high system drug levels are generally undesirable in lung targeted therapies, high blood levels in this rodent study could be indicative of increased pulmonary tissue exposure using BMP formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Strifler, Lisa; Veroniki, Areti-Angeliki; Yazdi, Fatemeh; Khan, Paul A; Scott, Alistair; Ng, Carmen; Antony, Jesmin; Mrklas, Kelly; D'Souza, Jennifer; Cardoso, Roberta; Straus, Sharon E

2015-10-26

To compare the safety and effectiveness of long-acting β-antagonists (LABA), long-acting antimuscarinic agents (LAMA) and inhaled corticosteroids (ICS) for managing chronic obstructive pulmonary disease (COPD). Systematic review and network meta-analysis (NMA). 208 randomised clinical trials (RCTs) including 134,692 adults with COPD. LABA, LAMA and/or ICS, alone or in combination, versus each other or placebo. The proportion of patients with moderate-to-severe exacerbations. The number of patients experiencing mortality, pneumonia, serious arrhythmia and cardiovascular-related mortality (CVM) were secondary outcomes. NMA was conducted including 20 RCTs for moderate-to-severe exacerbations for 26,141 patients with an exacerbation in the past year. 32 treatments were effective versus placebo including: tiotropium, budesonide/formoterol, salmeterol, indacaterol, fluticasone/salmeterol, indacaterol/glycopyrronium, tiotropium/fluticasone/salmeterol and tiotropium/budesonide/formoterol. Tiotropium/budesonide/formoterol was most effective (99.2% probability of being the most effective according to the Surface Under the Cumulative RAnking (SUCRA) curve). NMA was conducted on mortality (88 RCTs, 97 526 patients); fluticasone/salmeterol was more effective in reducing mortality than placebo, formoterol and fluticasone alone, and was the most effective (SUCRA=71%). NMA was conducted on CVM (37 RCTs, 55,156 patients) and the following were safest: salmeterol versus each OF placebo, tiotropium and tiotropium (Soft Mist Inhaler (SMR)); fluticasone versus tiotropium (SMR); and salmeterol/fluticasone versus tiotropium and tiotropium (SMR). Triamcinolone acetonide was the most harmful (SUCRA=81%). NMA was conducted on pneumonia occurrence (54 RCTs, 61 551 patients). 24 treatments were more harmful, including 2 that increased risk of pneumonia versus placebo; fluticasone and fluticasone/salmeterol. The most harmful agent was fluticasone/salmeterol (SUCRA=89%). NMA was conducted for arrhythmia; no statistically significant differences between agents were identified. Many inhaled agents are available for COPD, some are safer and more effective than others. Our results can be used by patients and physicians to tailor administration of these agents. PROSPERO # CRD42013006725. 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/

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 firing point and is promoted by an inhaled flow rate of up to 90 l/min-that is, the slow and medium setting used in these studies. PMID:7638806

Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium

PubMed Central

2015-01-01

Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment. PMID:24811243

[Preoperative Management of Patients with Bronchial Asthma or Chronic Bronchitis].

PubMed

Hagihira, Satoshi

2015-09-01

Bronchial asthma is characterized by chronic airway inflammation. The primary goal of treatment of asthma is to maintain the state of control. According to the Japanese guidelines (JGL2012), long-term management consists of 4 therapeutic steps, and use of inhaled corticosteroids (ICS) is recommended at all 4 steps. Besides ICS, inhalation of long-acting β2-agonist (LABA) is also effective. Recently, omalizumab (a humanized antihuman IgE antibody) can be available for patients with severe allergic asthma. Although there is no specific strategy for preoperative treatment of patients with asthma, preoperative systemic steroid administration seemed to be effective to prevent asthma attack during anesthesia. The most common cause of chronic bronchitis is smoking. Even the respiratory function is within normal limits, perioperative management of patients with chronic bronchitis is often troublesome. The most common problem is their sputum. To minimize perioperative pulmonary complication in these patients, smoking cessation and pulmonary rehabilitation are essential. It is known that more than 1 month of smoking cessation is required to reduce perioperative respiratory complication. However, even one or two weeks of smoking cessation can decrease sputum secretion. In summary, preoperative optimization is most important to prevent respiratory complication in patients with bronchial asthma or chronic bronchitis.

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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Web-based multimedia vignettes in advanced community pharmacy practice experiences.

PubMed

Flowers, Schwanda K; Vanderbush, Ross E; Hastings, Jan K; West, Donna

2010-04-12

To evaluate the effectiveness of Web-based multimedia vignettes on complex drug administration techniques to augment the training of pharmacy students in advanced community pharmacy practice experiences. During the orientation for a community APPE, students were randomly assigned to either a study group or control group After they began their APPE, students in the study group were given an Internet address to access multimedia vignettes which they were required to watch to augment their training and standardize their counseling of patients in the use of inhalers and ear and eye drops. A 12-item questionnaire was administered to students in both groups at the orientation and again on the last day of the APPE to evaluate their knowledge of counseling patients in the use of inhalers and ear and eye drops. The control group did not experience any improvement in their counseling knowledge of the research topics during their month-long experience. Students in the intervention group scored higher on their postintervention test than students in the control group (p < 0.001). Student learning outcomes from experiential training can be improved through the use of Web-based multimedia instructional vignettes.

In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.

PubMed

Möller, L

1994-10-01

During incomplete combustion of organic matter, nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), are formed in a reaction that is catalyzed by a low pH. 2-Nitrofluorene (NF), a marker for nitro-PAHs, is metabolized in vivo by two different routes. After inhalation, potent mutagenic metabolites, hydroxylated nitrofluorenes (OH-NFs), are formed. The metabolites are distributed by systemic circulation. After oral administration, NF is reduced to the corresponding amine, a reaction mediated by the intestinal microflora. This metabolite is acetylated to 2-acetylaminofluorene (AAF), a potent carcinogen. Further ring-hydroxylation of AAF leads to detoxification and excretion. Induction of cytochrome P450s affects the metabolism, and more OH-NFs are formed. As a consequence, more mutagenic metabolites are found in the circulation. OH-NFs are excreted in the bile as, in terms of mutagenicity, totally harmless glucuronide conjugates. When these conjugates are excreted via the bile, intestinal beta-glucuronidase can liberate direct-acting mutagens in the intestine. Thus, inhalation of NF can lead to formation of potent mutagens in the intestine. NF is a direct-acting mutagen in bacterial assays and an initiator and promoter of the carcinogenic process, and gives rise to DNA adduct formation in laboratory animals.

Inhalant Abuse and Dextromethorphan.

PubMed

Storck, Michael; Black, Laura; Liddell, Morgan

2016-07-01

Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies on the Inhalation Toxicity of Dyes Present in Colored Smoke Munitions. Phase III, Studies: Four-Week Inhalation Exposures of Rats to Dye Aerosols.

DTIC Science & Technology

1984-09-10

0") AD STUDIES ON THE INHALATION TOXICITY CO• OF DYES PRESENT IN COLORED Ln SMOKE MUNIlIONS U FINAL REPORT FOR PHASE III STUDIES : SFOUR- ELK...3 RECIIEPIT’S CATA6.0G NUMBE.• 4. TITLE (and ,ubiltI.e) S. TYPE OF REPORT & PERIOD COygC r., Studies on the Inhalation Toxicity of Dyes Final: Phase...III Present in Colored Smoke Munitions. Final Report Fh for Phase 111 Studies : FoLr-Week Inhalation G. PERFORMING ORO. REPORT N,’,ER Exposures of Rats

Timing of dornase alfa inhalation for cystic fibrosis.

PubMed

Dentice, Ruth; Elkins, Mark

2016-07-26

Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review. To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms. The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.

Zanamivir Oral Inhalation

MedlinePlus

... prescribed by your doctor.Zanamivir comes with a plastic inhaler called a Diskhaler (device for inhaling powder) ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

Mometasone Oral Inhalation

MedlinePlus

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

Control of ethanol withdrawal symptoms in mice by phenytoin.

PubMed

Sprague, G L; Craigmill, A L

1976-12-01

Mice were made physically dependent upon ethanol using either of two methods which involved ethanol vapor inhalation. Following the cessation of exposure to ethanol, the severity of handling-induced convulsions and changes in the response to an electric foot shock (startle reflex) were recorded. Animals given isotonic saline or propylene glycol:ethanol vehicle during withdrawal exhibited handling-induced convulsions, and ethanol (2.0-4.0 g/kg) or phenytoin (5-20 mg/kg) administration during withdrawal resulted in a reduction in the severity of these convulsions. A reduced startle reflex threshold was also evident during withdrawal in mice given isotonic saline or propylene glycol:ethanol vehicle. Ethanol (0.5-4.0 g/kg) or phenytoin (10-20 mg/kg) administration during withdrawal resulted in a significant elevation of the startle reflex threshold compared to control animals. The results are discussed as they relate to others obtained in experimental and clinical studies.

Intratracheal Milrinone Bolus Administration During Acute Right Ventricular Dysfunction After Cardiopulmonary Bypass.

PubMed

Gebhard, Caroline Eva; Desjardins, Georges; Gebhard, Cathérine; Gavra, Paul; Denault, André Y

2017-04-01

To evaluate intratracheal milrinone (tMil) administration for rapid treatment of right ventricular (RV) dysfunction as a novel route after cardiopulmonary bypass. Retrospective analysis. Single-center study. The study comprised 7 patients undergoing cardiac surgery who exhibited acute RV dysfunction after cardiopulmonary bypass. After difficult weaning caused by cardiopulmonary bypass-induced acute RV dysfunction, milrinone was administered as a 5-mg bolus inside the endotracheal tube. RV function improvement, as indicated by decreasing pulmonary artery pressure and changes of RV waveforms, was observed in all 7 patients. Adverse effects of tMil included dynamic RV outflow tract obstruction (2 patients) and a decrease in systemic mean arterial pressure (1 patient). tMil may be an effective, rapid, and easily applicable therapeutic alternative to inhaled milrinone for the treatment of acute RV failure during cardiac surgery. However, sufficiently powered clinical trials are needed to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcium and zinc DTPA administration for internal contamination with plutonium-238 and americium-241.

PubMed

Kazzi, Ziad N; Heyl, Alexander; Ruprecht, Johann

2012-08-01

The accidental or intentional release of plutonium or americium can cause acute and long term adverse health effects if they enter the human body by ingestion, inhalation, or injection. These effects can be prevented by rapid removal of these radionuclides by chelators such as calcium or zinc diethylenetriaminepentaacetate (calcium or zinc DTPA). These compounds have been shown to be efficacious in enhancing the elimination of members of the actinide family particularly plutonium and americium when administered intravenously or by nebulizer. The efficacy and adverse effects profile depend on several factors that include the route of internalization of the actinide, the type, and route time of administration of the chelator, and whether the calcium or zinc salt of DTPA is used. Current and future research efforts should be directed at overcoming limitations associated with the use of these complex drugs by using innovative methods that can enhance their structural and therapeutic properties.

Feasibility of Deploying Inhaler Sensors to Identify the Impacts of Environmental Triggers and Built Environment Factors on Asthma Short-Acting Bronchodilator Use.

PubMed

Su, Jason G; Barrett, Meredith A; Henderson, Kelly; Humblet, Olivier; Smith, Ted; Sublett, James W; Nesbitt, LaQuandra; Hogg, Chris; Van Sickle, David; Sublett, James L

2017-02-01

Epidemiological asthma research has relied upon self-reported symptoms or healthcare utilization data, and used the residential address as the primary location for exposure. These data sources can be temporally limited, spatially aggregated, subjective, and burdensome for the patient to collect. First, we aimed to test the feasibility of collecting rescue inhaler use data in space-time using electronic sensors. Second, we aimed to evaluate whether these data have the potential to identify environmental triggers and built environment factors associated with rescue inhaler use and to determine whether these findings would be consistent with the existing literature. We utilized zero-truncated negative binomial models to identify triggers associated with inhaler use, and implemented three sensitivity analyses to validate our findings. Electronic sensors fitted on metered dose inhalers tracked 5,660 rescue inhaler use events in space and time for 140 participants from 13 June 2012 to 28 February 2014. We found that the inhaler sensors were feasible in passively collecting objective rescue inhaler use data. We identified several environmental triggers with a positive and significant association with inhaler use, including: AQI, PM10, weed pollen, and mold. Conversely, the spatial distribution of tree cover demonstrated a negative and significant association with inhaler use. Utilizing a sensor to capture the signal of rescue inhaler use in space-time offered a passive and objective signal of asthma activity. This approach enabled detailed analyses to identify environmental triggers and built environment factors that are associated with asthma symptoms beyond the residential address. The application of these new technologies has the potential to improve our surveillance and understanding of asthma. Citation: Su JG, Barrett MA, Henderson K, Humblet O, Smith T, Sublett JW, Nesbitt L, Hogg C, Van Sickle D, Sublett JL. 2017. Feasibility of deploying inhaler sensors to identify the impacts of environmental triggers and built environment factors on asthma short-acting bronchodilator use. Environ Health Perspect 125:254-261; http://dx.doi.org/10.1289/EHP266.

Inhaled nitric oxide, oxygen, and alkalosis: dose-response interactions in a lamb model of pulmonary hypertension.

PubMed

Heidersbach, R S; Johengen, M J; Bekker, J M; Fineman, J R

1999-07-01

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1-6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). Systemic arterial pressure remained unchanged. At 5 ppm of inhaled NO, alkalosis and oxygen induced further dose-dependent decreases in mean pulmonary arterial pressures (P < 0.05). At inhaled NO doses > 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH > 7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 > 0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies.

Long-Acting β-Agonist in Combination or Separate Inhaler as Step-Up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids.

PubMed

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

Adding a long-acting β 2 -agonist (LABA) to inhaled corticosteroids (ICS) using a fixed-dose combination (FDC) inhaler is the UK guideline recommendation for children aged more than 4 years with uncontrolled asthma. The evidence of benefit of adding an FDC inhaler over a separate LABA inhaler is limited. The objective of this study was to compare the effectiveness of a LABA added as an FDC inhaler, and as a separate inhaler, in children with uncontrolled asthma. Two UK primary care databases were used to create a matched cohort study with a 2-year follow-up period. We included children prescribed their first step-up from ICS monotherapy. Two cohorts were formed for children receiving an add-on LABA as an FDC inhaler, or a separate LABA inhaler. Matching variables and confounders were identified by comparing characteristics during a baseline year of follow-up. Outcomes were examined during the subsequent year. The primary outcome was an adjusted odds ratio for overall asthma control (defined as follows: no asthma-related hospital admission or emergency room visit, prescription for oral corticosteroids or antibiotic with evidence of respiratory consultation, and ≤2 puffs of short-acting β-agonist daily). The final study consisted of 1330 children in each cohort (mean age 9 years; 59% male). In the separate ICS+LABA cohort, the odds of achieving overall asthma control were lower (adjusted odds ratio, 0.77 [95% confidence interval, 0.66-0.91]; P = .001) compared with the FDC cohort. The study demonstrates a small but significant benefit in achieving asthma control from an add-on LABA as an FDC, compared with a separate inhaler and this supports current guideline recommendations. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Inhalants in Peru.

PubMed

Lerner, R; Ferrando, D

1995-01-01

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

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.

A cross-sectional questionnaire study of the rules governing pupils' carriage of inhalers for asthma treatment in secondary schools in North East England.

PubMed

Funston, Wendy; Howard, Simon J

2016-01-01

Objectives. The primary objective of this study was to assess the rules governing secondary school pupils' carriage of inhalers for emergency treatment of asthma in the North East of England. Design. This study was based upon a postal questionnaire survey. Setting. The setting for this study was mainstream free-to-attend secondary schools which admit 16 year old pupils within the 12 Local Authority areas which make up the North East of England. Participants. All 153 schools meeting the inclusion criteria were invited to participate in the study, of which 106 (69%) took part. Main Outcome Measures. Our three main outcome measures were: whether pupils are permitted to carry inhalers on their person while at school; whether advance permission is required for pupils to carry inhalers, and from whom; and whether the school has an emergency 'standby' salbutamol inhaler for use in asthma emergencies, as permitted since October 2014 under recent amendments to The Human Medicines Regulations 2012. Results. Of 98 schools submitting valid responses to the question, 99% (n = 97) permitted pupils to carry inhalers on their person while at school; the remaining school stored pupils' inhalers in a central location within the school. A total of 22% of included schools (n = 22) required parental permission before pupils were permitted to carry inhalers. Of 102 schools submitting valid responses to the question, 44% (n = 45) had purchased a 'standby' salbutamol inhaler for use in asthma emergencies. Conclusions. Most secondary schools in North East England permit pupils to carry inhalers on their person. The requirement in a minority of schools for parental permission to be given possibly contravenes the standard ethical practices in clinical medicine for children of this age. Only a minority of schools hold a 'standby' salbutamol inhaler for use in asthma emergencies. Wider availability may improve outcomes for asthma emergencies occurring in schools.

An Acoustic-Based Method to Detect and Quantify the Effect of Exhalation into a Dry Powder Inhaler.

PubMed

Holmes, Martin S; Seheult, Jansen N; O'Connell, Peter; D'Arcy, Shona; Ehrhardt, Carsten; Healy, Anne Marie; Costello, Richard W; Reilly, Richard B

2015-08-01

Dry powder inhaler (DPI) users frequently exhale into their inhaler mouthpiece before the inhalation step. This error in technique compromises the integrity of the drug and results in poor bronchodilation. This study investigated the effect of four exhalation factors (exhalation flow rate, distance from mouth to inhaler, exhalation duration, and relative air humidity) on dry powder dose delivery. Given that acoustic energy can be related to the factors associated with exhalation sounds, we then aimed to develop a method of identifying and quantifying this critical inhaler technique error using acoustic based methods. An in vitro test rig was developed to simulate this critical error. The effect of the four factors on subsequent drug delivery were investigated using multivariate regression models. In a further study we then used an acoustic monitoring device to unobtrusively record the sounds 22 asthmatic patients made whilst using a Diskus(™) DPI. Acoustic energy was employed to automatically detect and analyze exhalation events in the audio files. All exhalation factors had a statistically significant effect on drug delivery (p<0.05); distance from the inhaler mouthpiece had the largest effect size. Humid air exhalations were found to reduce the fine particle fraction (FPF) compared to dry air. In a dataset of 110 audio files from 22 asthmatic patients, the acoustic method detected exhalations with an accuracy of 89.1%. We were able to classify exhalations occurring 5 cm or less in the direction of the inhaler mouthpiece or recording device with a sensitivity of 72.2% and specificity of 85.7%. Exhaling into a DPI has a significant detrimental effect. Acoustic based methods can be employed to objectively detect and analyze exhalations during inhaler use, thus providing a method of remotely monitoring inhaler technique and providing personalized inhaler technique feedback.

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

The Contributing Risk of Tobacco Use for ARDS Development in Burn-Injured Adults With Inhalation Injury.

PubMed

Afshar, Majid; Netzer, Giora; Mosier, Michael J; Cooper, Richard S; Adams, William; Burnham, Ellen L; Kovacs, Elizabeth J; Durazo-Arvizu, Ramon; Kliethermes, Stephanie

2017-11-01

This study aims to determine the relationship between tobacco use, inhalation injury, and ARDS in burn-injured adults. This study was an observational cohort of 2,485 primary burn admissions to a referral burn center between January 1, 2008 and March 15, 2015. Subjects were evaluated by methods used to account for mediation and traditional approaches (multivariable logistic regression and propensity score analysis). Mediation analysis examined both the (1) indirect effect of tobacco use via inhalation injury as the mediator on ARDS development and (2) the direct effect of tobacco use alone on ARDS development. ARDS development occurred in 6.8% ( n = 170) of the cohort. Inhalation injury occurred in 5.0% ( n = 125) of the cohort, and ARDS developed in 48.8% ( n = 83) of the subjects with inhalation injury. Tobacco use was 2-fold more common in subjects with ARDS. In the mediated model, the direct effect of tobacco use on ARDS, including interaction between tobacco use and inhalation injury, was not significant (odds ratio [OR] 1.63, 95% CI 0.91-2.92, P = .10). However, the indirect effect of tobacco use via inhalation injury as the mediator was significant (OR 1.61, 95% CI 1.25-2.07, P < .001), and the proportion of the total effect of tobacco use operating through the mediator was 55.6%. In the non-mediation models (multivariable logistic regression and propensity score analysis), which controlled for inhalation injury and other covariables, the OR for the association between tobacco use and ARDS was 1.84 (95% CI 1.22-2.81, P < .001) and 1.69 (95% CI 1.04-2.75, P = .03), respectively. In mediation analysis, inhalation injury was the overwhelming predictor for ARDS development, whereas tobacco use has its strongest effect indirectly through inhalation injury. Patients with at least moderate inhalation injury are at greatest risk for ARDS development despite baseline risk factors like tobacco use. Copyright © 2017 by Daedalus Enterprises.

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

Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone.

PubMed

Fukushima, Chizu; Matsuse, Hiroto; Tomari, Shinya; Obase, Yasushi; Miyazaki, Yoshitsugu; Shimoda, Terufumi; Kohno, Shigeru

2003-06-01

Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play a central role in the treatment of bronchial asthma. Fluticasone exhibits excellent clinical effectiveness; however, oral adverse effects can occur. To compare the frequency of oral candidiasis in asthmatic patients treated with fluticasone and beclomethasone, to evaluate the effect of gargling with amphotericin B, and to measure the inhalation flow rate on candidiasis. The study consisted of 143 asthmatic patients who were treated with inhaled steroids, 11 asthmatic patients not treated with inhaled steroids, and 86 healthy volunteers. Quantitative fungal culture was performed by aseptically obtaining a retropharyngeal wall swab from these patients. Patients with positive results were treated with gargling using a 1:50 dilution amphotericin B solution. In asthmatic patients treated with fluticasone, the inhalation flow rate was measured using an inspiratory flow meter. The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone. Gargling with amphotericin B was effective in most asthmatic patients with candidiasis. Candidiasis was not due to inappropriate flow rates during inhalation of steroids. Fungal culture of a retropharyngeal wall swab may be useful for predicting the risk of developing oral candidiasis in asthmatic patients treated with inhaled steroids. The amount of isolated Candida was significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Attention to dosage is required as the amount of Candida increased with dose of fluticasone. Gargling with a 1:50 dilution of amphotericin B is effective in treating oral candidiasis of asthmatic patients treated with inhaled steroids.

Biological relevance of effects following chronic administration of octamethylcyclotetrasiloxane (D4) in Fischer 344 rats.

PubMed

Dekant, Wolfgang; Scialli, Anthony R; Plotzke, Kathy; Klaunig, James E

2017-10-20

Octamethylcyclotetrasiloxane (D4) is a cyclic siloxane primarily used as a monomer or intermediate in the production of silicone polymers resulting in potential exposure of workers, and potential low level inhalation or dermal exposure for consumers and the general public. Following a two-year inhalation toxicity study with D4 in rats, increases in uterine endometrial cystic hyperplasia and adenomas were observed at the highest concentration of D4 administered (700ppm). No other neoplasms were increased with D4 treatment. In addition, chronic inhalation exposure of rats to D4 induced changes in relative liver and kidney weights, and produced a chronic nephropathy. This manuscript examines the biological relevance and possible modes of action for the effects observed in the F344 rat following chronic inhalation exposure to D4. D4 is not genotoxic and appears to exert its effects through a nongenotoxic mode of action. An alteration in the estrous cycle in the aging F344 rat was the most likely mode of action for the observed uterine effects following chronic inhalation exposure. Data support the conclusion that D4 acts indirectly via a dopamine-like mechanism leading to alteration of the pituitary control of the estrous cycle in aging F344 rats with a decrease in progesterone and an increase in the estrogen/progesterone ratio most likely induced by a decrease in prolactin concentration. D4 also inhibited the pre-ovulatory LH surge causing a delay in ovulation, persistent follicles and thus a prolonged exposure to elevated estrogen in the adult Sprague Dawely rat. A lengthening of the estrous cycle in the F344 rat with an increase in endogenous estrogen was also induced by D4 inhalation. Although the mode of action responsible for induction of uterine adenomas in the female F344 rat has not been clearly confirmed, the subtlety of effects on the effects of D4 on cyclicity may prevent further assessment and definition of the mode of action. The occurrence of uterine endometrial adenoma in the rat is not relevant for human risk characterization because (1) there are differences in ovulatory cycle regulation in rats compared to humans, (2) cystic hyperplasia without atypia in women is not a cancer precursor, and (3) there is no endometrial lesion in women that is directly analogous to endometrial adenoma in the rat. The effects of D4 on liver are due to a phenobarbital-like mechanism that results in induction of cytochrome P450 and other enzymes of xenobiotic biotransformation. The liver effects are adaptive and not adverse. Kidney findings included chonic progressive nephropathy, a rat lesion that has no counterpart in the human and that should not be used in human risk assessment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler

PubMed Central

Golshahi, Laleh; Behara, Srinivas R.B.; Tian, Geng; Farkas, Dale R.; Hindle, Michael

2015-01-01

Abstract Purpose: Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy. Methods: The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region. Results: The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5–2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%. Conclusions: The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy. PMID:25192072

Optimizing identification and management of COPD patients - reviewing the role of the community pharmacist.

PubMed

van der Molen, Thys; van Boven, Job F M; Maguire, Terence; Goyal, Pankaj; Altman, Pablo

2017-01-01

The aim of this paper was to propose key steps for community pharmacist integration into a patient care pathway for chronic obstructive pulmonary disease (COPD) management. A literature search was conducted to identify publications focusing on the role of the community pharmacist in identification and management of COPD. The literature search highlighted evidence supporting an important role for pharmacists at each of the four key steps in the patient care pathway for COPD management. Step 1 (primary prevention): pharmacists are ideally placed to provide information on disease awareness and risk prevention campaigns, and to encourage lifestyle interventions, including smoking cessation. Step 2 (early detection/case finding): pharmacists are often the first point of contact between the patient and the healthcare system and can therefore play an important role in the early identification of patients with COPD. Step 3 (management and ongoing support): pharmacists can assist patients by providing advice and education on dosage, inhaler technique, treatment expectations and the importance of adherence, and by supporting self-management, including recognition and treatment of COPD exacerbations. Step 4 (review and follow-up): pharmacists can play an important role in monitoring adherence and ongoing inhaler technique in patients with COPD. In summary, pharmacists are ideally positioned to play a vital role in all key stages of an integrated COPD patient care pathway from early disease detection to the support of management plans, including advice and counselling regarding medications, inhaler technique and treatment adherence. Areas requiring additional consideration include pharmacist training, increasing awareness of the pharmacist role, administration and reimbursement, and increasing physician-pharmacist collaboration. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Nitrous oxide/oxygen inhalation provides effective analgesia during the administration of tumescent local anaesthesia for endovenous laser ablation.

PubMed

Meier, Thomas Oleg; Jacomella, Vincenzo; Clemens, Robert Karl Josef; Amann-Vesti, Beatrice

2015-11-01

Tumescent anaesthesia (TA) is an important but sometimes very painful step during endovenous thermal ablation of incompetent veins. The aim of this study was to examine whether the use of fixed 50% nitrous oxide/oxygen mixture (N2O/O2), also called equimolar mixture of oxygen and nitrous oxide, reduces pain during the application of TA. Patients undergoing endovenous laser ablation (EVLA) of incompetent saphenous veins were included. Thirty consecutive patients inhaled N2O/O2 during the application of TA. Thirty consecutive patients received TA alone (controls). Patients were asked to complete a questionnaire immediately after the intervention to assess satisfaction with the intervention and pain-levels during the different steps of the intervention (0=not at all, 10=very much). Adverse events during the treatment were monitored. 30 patients (14 men, mean age of 44 years) were included in the N2O/O2 group and 30 patients (9 men, mean age 48 years) were included in the control group. In the N2O/O2 group a significantly lower pain score was noted (mean 2.45 points, range 0-6) compared to the controls (mean 4.3 points, range 1-9, p<0.001). Overall, 64.5% of the patients were perfectly satisfied with the N2O/O2-Inhalation. Only 4 patients receiving N2O/O2 complained of adverse effects such as unpleasant loss of control (2 patients), headache (1 patient) and dizziness (1 patient). N2O/O2 is a safe and effective method to reduce pain during the application of tumescent anaesthesia for EVLA.