WorldWideScience

Sample records for vivo inhalation gas

  1. Chlorine Gas Inhalation

    Science.gov (United States)

    White, Carl W.; Martin, James G.

    2010-01-01

    Humans can come into contact with chlorine gas during short-term, high-level exposures due to traffic or rail accidents, spills, or other disasters. By contrast, workplace and public (swimming pools, etc.) exposures are more frequently long-term, low-level exposures, occasionally punctuated by unintentional transient increases. Acute exposures can result in symptoms of acute airway obstruction including wheezing, cough, chest tightness, and/or dyspnea. These findings are fairly nonspecific, and might be present after exposures to a number of inhaled chemical irritants. Clinical signs, including hypoxemia, wheezes, rales, and/or abnormal chest radiographs may be present. More severely affected individuals may suffer acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Up to 1% of exposed individuals die. Humidified oxygen and inhaled β-adrenergic agents are appropriate therapies for victims with respiratory symptoms while assessments are underway. Inhaled bicarbonate and systemic or inhaled glucocorticoids also have been reported anecdotally to be beneficial. Chronic sequelae may include increased airways reactivity, which tends to diminish over time. Airways hyperreactivity may be more of a problem among those survivors that are older, have smoked, and/or have pre-existing chronic lung disease. Individuals suffering from irritant-induced asthma (IIA) due to workplace exposures to chlorine also tend to have similar characteristics, such as airways hyperresponsiveness to methacholine, and to be older and to have smoked. Other workplace studies, however, have indicated that workers exposed to chlorine dioxide/sulfur dioxide have tended to have increased risk for chronic bronchitis and/or recurrent wheezing attacks (one or more episodes) but not asthma, while those exposed to ozone have a greater incidence of asthma. Specific biomarkers for acute and chronic exposures to chlorine gas are currently lacking. Animal models for chlorine gas

  2. Suicide by Inhalation of Suffocative Gas

    Directory of Open Access Journals (Sweden)

    Yalçın Büyük

    2005-12-01

    Full Text Available LPG is a by-product of petroleum refining and is a colourless gas with a mild odour. A foul odorant such as ethanethiol is added before commercially presented. LPG is highly flammable and has a high fire and explosive hazard. LPG is commercially available as propane, butane and propane-butane mixtures. Propane is a colourless and odourless flammable gas. Butane is a colourless and flammable gas with a gasoline-like or natural gas odour. Suicide by LPG inhalation was relatively common due to widespread availability of installation systems. Currently suicide by inhalation of these gases is rare due to changing trends, and only a few case reports about death following accidental or intentional inhalation of LPG have been reported recently. Sudden death due to inhalation of these gases in abusers is the most encountered condition. This case report is about a 65 years old man found dead in his bed holding a LPG tube near his mouth and nose. Inhalation of suffocative gas was determined to be the cause of death based on autopsy findings and the scene investigation. This paper discusses the medico-legal approach for this type of intoxication cases. Key words: LPG, butane, propane, suicide, autopsy

  3. Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic modeling for in vivo inhalation gas uptake data exposure in female B6C3F1 mice.

    Science.gov (United States)

    Evans, M V; Caldwell, J C

    2010-05-01

    Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools for calculation of internal and target organ doses of parent compound and metabolites. PBPK models, coupled with in vivo inhalation gas-uptake data, can be useful to estimate total metabolism. Previously, such an approach was used to make predictions regarding the metabolism and to make subsequent inferences of DCM's mode of action for toxicity. However, current evidence warrants re-examination of this approach. The goal of this work was to examine two different hypotheses for DCM metabolism in mice. One hypothesis describes two metabolic pathways: one involving cytochrome P450 2E1 (CYP2E1) and a second glutathione (GSH). The second metabolic hypothesis describes only one pathway mediated by CYP2E1 that includes multiple binding sites. The results of our analysis show that the in vivo gas-uptake data fit both hypotheses well and the traditional analysis of the chamber concentration data is not sufficient to distinguish between them. Gas-uptake data were re-analyzed by construction of a velocity plot as a function of increasing DCM initial concentration. The velocity (slope) analysis revealed that there are two substantially different phases in velocity, one rate for lower exposures and a different rate for higher exposures. The concept of a "metabolic switch," namely that due to conformational changes in the enzyme after one site is occupied - a different metabolic rate is seen - is also consistent with the experimental data. Our analyses raise questions concerning the importance of GSH metabolism for DCM. Recent research results also question the importance of this pathway in the toxicity of DCM. GSH-related DNA adducts were not formed after in vivo DCM exposure in mice and DCM-induced DNA damage has

  4. Inhalants

    Science.gov (United States)

    ... of inhalants, visit http://www.drugabuse.gov/drugs-abuse/inhalants . Do people use inhalants for breathing problems? No, they use inhalers, which usually contain a type of steroid that reduces inflammation in the airways. Or they ...

  5. Development and evaluation of an inhalation chamber for in vivo tests

    Directory of Open Access Journals (Sweden)

    EDUARDO R. DA SILVA

    2017-08-01

    Full Text Available ABSTRACT The bioavailability, toxicity, and therapeutic efficacy of a drug is directly related to its administration route. The pulmonary route can be accessed by inhalation after fumigation, vaporization or nebulization. Thus, pharmacological and toxicological evaluation accessed by an apparatus specifically designed and validated for this type of administration is extremely important. Based on pre-existing models, an inhalation chamber was developed. This presents a central structure with five animal holders. The nebulized air passes directly and continuously through these holders and subsequently to an outlet. Evaluation of its operation was performed using clove essential oil, a nebulizer, and a flow meter. The air within the chamber was collected by static headspace and analyzed by gas chromatography with a flame ionization detector. For this purpose, a 2.5 minutes chromatographic method was developed. The air flow in each of the five outputs was 0.92 liters per minute. During the first minute, the chamber became saturated with the nebulized material. Homogeneous and continuous operation of the chamber was observed without accumulation of volatile material inside it for 25 minutes. The inhalation chamber works satisfactorily for in vivo tests with medicines designed to be administrated by inhalation.

  6. Mass casualties from acute inhalation of chlorine gas.

    Science.gov (United States)

    Cevik, Yunsur; Onay, Meral; Akmaz, Ibrahim; Sezigen, Sermet

    2009-12-01

    Chlorine gas is a potent pulmonary irritant that affects the mucous membranes and induces severe disturbances of pulmonary gas exchange within minutes of inhalation. The present study evaluated an extraordinary type of mass inhalational exposure. Clinical reports of 25 soldiers who were admitted to the emergency department of Maresal Cakmak Military Hospital, Erzurum were retrospectively evaluated. All patients were exposed to chlorine gas as a result of mixing sodium hypochlorite with hydrochloric acid during cleaning activities. All patients were male and the mean age of patients was 22.04+/-2.98 years. The main symptoms were coughing and dyspnea in 18 patients (72%). Forced expiratory volume in 1 second (FEV1) and FEV1/forced volume capacity (FVC) ratio were found to be normal in all patients but FVC and peak expiratory flow (PEF) were below the normal range (80%) in 9 patients (36%). All patients received warmed humidified oxygen combined with nebulized salbutamol. Inhaled budesonide and nebulized sodium bicarbonate were ordered additionally for 19 patients (76%). Thirteen patients (52%) were discharged from the emergency department and 12 patients (48%) were hospitalized. No mortality was observed. Chlorine gas is a potent pulmonary irritant that causes acute damage in both the upper and lower respiratory tract. We suggest that inhaled steroids combined with nebulized sodium bicarbonate could be a safe and effective alternative for the treatment of symptomatic patients. Education of the public about the dangers of mixing of hypochlorite bleach with acidic cleaning agents is also very important.

  7. Inhalants

    Science.gov (United States)

    ... containers, or rags or clothing soaked with chemicals drunk or disoriented actions slurred speech nausea (feeling sick) ... functions choking—inhaling vomit after inhalant use injuries—accidents, including driving, while intoxicated Are inhalants addictive? It ...

  8. Autoerotic accident by inhalation of propane-butane gas mixture.

    Science.gov (United States)

    Jackowski, Christian; Römhild, Wolfgang; Aebi, Beat; Bernhard, Werner; Krause, Dieter; Dirnhofer, Richard

    2005-12-01

    We present a case of an accidental autoerotic death involving the inhalation of a propane-butane gas mixture, also known as LPG (liquefied petroleum gas). A 19-year-old male was found dead in supine position in his bed in a residential accommodation one day after he was last seen alive. On a personal computer at the end of the bed, a pornographic movie was still running. On his left shoulder, an empty rubber balloon and on the bedside 2 empty "Kisag-Gas" cartridges were found. Toxicologic investigations revealed an intoxication with propane and butane, together with a recent consumption of cannabis. This case report compares the toxicologic findings with other recently published cases, and the theories of the toxic effects are discussed.

  9. Nitrous oxide inhalation anaesthesia in the presence of intraocular gas can cause irreversible blindness.

    Science.gov (United States)

    Lockwood, A J; Yang, Y F

    2008-03-08

    Nitrous oxide inhalation sedation is frequently used in dental and other surgical procedures. We report the case of a patient with intraocular gas who developed sudden elevation in intraocular pressure and blindness as a result of nitrous oxide anaesthesia. All medical and dental personnel administering nitrous oxide inhalation should be aware that this is contraindicated in patients with intraocular gas.

  10. Inhalants

    Science.gov (United States)

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

  11. Bronchial damage and diffuse alveolar hemorrhage following chlorine gas inhalation: A case report

    OpenAIRE

    Uemura, Kosuke; Isono, Momoko; Kagohashi, Katsunori; Hasegawa, Ryuichi; Satoh, Hiroaki

    2017-01-01

    Chlorine is a toxic inhalant and sources of exposure for individuals include accidental releases of chlorine vapor due to industrial or chemical transportation accidents. Inhalation of a large quantity of gas may cause circulatory and respiratory disorders or even mortality; however, the effects of a small amount of chlorine gas may be asymptomatic. The present case study presents a successfully treated 55‑year‑old male patient exposed to chlorine gas, resulting in bronchial damage and diffus...

  12. PLGA Ethionamide Nanoparticles for Pulmonary Delivery: Development and in vivo evaluation of dry powder inhaler.

    Science.gov (United States)

    Debnath, Sujit Kumar; Saisivam, Srinivasan; Omri, Abdelwahab

    2017-10-25

    PLGA (50:50) nanoparticles were prepared to sustain the release of Ethionamide in order to decrease the dose and dosing frequency. It further modified in the form of dry powder inhaler to make suitable for pulmonary administration and increase drug residency in lungs. Ethionamide loaded PLGA nanoparticles were prepared by solvent evaporation method. Freeze dried nanoparticles and anhydrous inhalable grade lactose were mixed manually using geometrical dilution process to modify the nanoparticles in the form of dry powder inhaler. Animal study was conducted to correlate between in-vivo and in-vitro. PLGA nanoparticles showed initial burst release followed by zero order release up to 95.17±3.59% in 24h. Aerodynamic particle size of optimized dry powder inhaler was found as 1.79μm. There was no significant aggregation of dry powder inhaler during 6 months of stability study. Area under the concentration-time curve from 0h to infinity (AUC0(-∞)) signifies the prolong residency of ETH in body compartment, revealed from animal study. PLGA 50:50 coated nanoparticles released Ethionamide for the period of 24h in simulated lungs fluid. Correlation between in-vitro dissolution and in-vivo study was established after performing animal study. Prepared dry powder inhaler maintained Ethionamide concentration above minimum inhibitory concentration for more than 12h after single dose administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Bronchial damage and diffuse alveolar hemorrhage following chlorine gas inhalation: A case report.

    Science.gov (United States)

    Uemura, Kosuke; Isono, Momoko; Kagohashi, Katsunori; Hasegawa, Ryuichi; Satoh, Hiroaki

    2017-11-01

    Chlorine is a toxic inhalant and sources of exposure for individuals include accidental releases of chlorine vapor due to industrial or chemical transportation accidents. Inhalation of a large quantity of gas may cause circulatory and respiratory disorders or even mortality; however, the effects of a small amount of chlorine gas may be asymptomatic. The present case study presents a successfully treated 55-year-old male patient exposed to chlorine gas, resulting in bronchial damage and diffuse alveolar hemorrhage. Endobronchial and alveolar injuries were evaluated by direct observation using fiberoptic bronchoscopy (FB) and analyzing bronchoalveolar lavage fluid obtained by FB. Taking a precise medical history from the patient is crucial to correctly diagnose toxic gas inhalation. In addition, a timely and proper evaluation with chest imaging as well as FB may provide useful clinical information. Therefore, clinicians should consider performing FB if the circumstances permit.

  14. Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment.

    Science.gov (United States)

    Stapleton, P A; McBride, C R; Yi, J; Nurkiewicz, T R

    2015-11-01

    With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO2 aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m(3), 5h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10(-4)M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats.

    Science.gov (United States)

    Matsuoka, Tadashi; Suzuki, Masaru; Sano, Motoaki; Hayashida, Kei; Tamura, Tomoyoshi; Homma, Koichiro; Fukuda, Keiichi; Sasaki, Junichi

    2017-09-01

    Mortality of hemorrhagic shock primarily depends on whether or not the patients can endure the loss of circulating volume until radical treatment is applied. We investigated whether hydrogen (H2) gas inhalation would influence the tolerance to hemorrhagic shock and improve survival. Hemorrhagic shock was achieved by withdrawing blood until the mean arterial blood pressure reached 30-35 mm Hg. After 60 minutes of shock, the rats were resuscitated with a volume of normal saline equal to four times the volume of shed blood. The rats were assigned to either the H2 gas (1.3% H2, 26% O2, 72.7% N2)-treated group or the control gas (26% O2, 74% N2)-treated group. Inhalation of the specified gas mixture began at the initiation of blood withdrawal and continued for 2 hours after fluid resuscitation. The survival rate at 6 hours after fluid resuscitation was 80% in H2 gas-treated rats and 30% in control gas-treated rats (p gas-treated rats than in the control rats. Despite losing more blood, the increase in serum potassium levels was suppressed in the H2 gas-treated rats after 60 minutes of shock. Fluid resuscitation completely restored blood pressure in the H2 gas-treated rats, whereas it failed to fully restore the blood pressure in the control gas-treated rats. At 2 hours after fluid resuscitation, blood pressure remained in the normal range and metabolic acidosis was well compensated in the H2 gas-treated rats, whereas we observed decreased blood pressure and uncompensated metabolic acidosis and hyperkalemia in the surviving control gas-treated rats. H2 gas inhalation delays the progression to irreversible shock. Clinically, H2 gas inhalation is expected to stabilize the subject until curative treatment can be performed, thereby increasing the probability of survival after hemorrhagic shock.

  16. Myocardial infarction, acute ischemic stroke, and hyperglycemia triggered by acute chlorine gas inhalation.

    Science.gov (United States)

    Kose, Ataman; Kose, Beril; Açikalin, Ayça; Gunay, Nurullah; Yildirim, Cuma

    2009-10-01

    Chlorine is one of the most common substances involved in toxic inhalation. Until now, several accidental exposures have been reported. The damage to the respiratory tract in the immediate phase after exposure to chlorine is well defined. Death occurs particularly due to pulmonary edema with respiratory failure and circulatory collapse. On the other hand, no association with myocardial infarction, acute stroke, severe hyperglycemia, and acute chlorine inhalation has been reported in literature. In the present study, an elderly (74-year-old) and diabetic case with myocardial infarction, acute stroke, hyperglycemia, and respiratory failure associated with acute chlorine intoxication after a diagnosis of acute chlorine poisoning and treatment in the emergency department is reported and the literature is revisited. Physicians should know that in elderly patients with a systemic disease who apply with chlorine gas inhalation, more serious complications along with damage in respiratory tract might be observed.

  17. β2-Adrenoreceptor Agonist Inhalation During Ex Vivo Lung Perfusion Attenuates Lung Injury.

    Science.gov (United States)

    Kondo, Takeshi; Chen, Fengshi; Ohsumi, Akihiro; Hijiya, Kyoko; Motoyama, Hideki; Sowa, Terumasa; Ohata, Keiji; Takahashi, Mamoru; Yamada, Tetsu; Sato, Masaaki; Aoyama, Akihiro; Date, Hiroshi

    2015-08-01

    Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that β2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that β2-adrenoreceptor agonist inhalation during ex vivo lung perfusion (EVLP) after procurement might also have a protective effect. Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the β2 group (receiving an aerosolized β2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n = 7) and the control group (receiving an aerosolized control solvent at the same time point; n = 6). Physiologic data, including lung function, were evaluated during EVLP. The β2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the β2 group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the β2 group than in the control group. The β2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. After procurement, β2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo.

    Science.gov (United States)

    Oei, Gezina T M L; Smit, Kirsten F; vd Vondervoort, Djai; Brevoord, Daniel; Hoogendijk, Arjan; Wieland, Catharina W; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2012-09-24

    Helium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific "conditioning" protocols. Before widespread use of this "conditioning" agent in clinical practice, negative side effects have to be ruled out. We investigated the effect of prolonged helium inhalation on the responsiveness of the human immune response in whole blood ex vivo. Male healthy volunteers inhaled 30 minutes heliox (79%He/21%O(2)) or air in a cross over design, with two weeks between measurements. Blood was withdrawn at T0 (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not incubated (0 h). An additional group of six volunteers inhaled 60 minutes of heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ) and interleukin-2 (IL-2) was analyzed by cytometric bead array. Statistical analysis was performed by the Wilcoxon test for matched samples. Incubation with LPS, LTA or TCS significantly increased TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone. Thirty min of helium inhalation did not influence the amounts of TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to air. Sixty min of helium inhalation did not affect cytokine production after LPS stimulation. We conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers. Dutch Trial Register: http://www.trialregister.nl/ NTR2152.

  19. Ataxia with Parkinsonism and dystonia after intentional inhalation of liquefied petroleum gas

    Directory of Open Access Journals (Sweden)

    Godani M

    2015-05-01

    Full Text Available Massimiliano Godani,1 Francesca Canavese,1 Sonia Migliorini,2 Massimo Del Sette1 1Neurology Unit, 2Department of Neuroradiology, Sant’Andrea Hospital, La Spezia, Italy Abstract: The practice of inhaling liquefied petroleum gas (LPG to commit suicide is uncommon and almost exclusively a prerogative of the prison population. Numerous cases of sudden deaths caused by intentional propane and/or butane inhalation have been described, but these cases survived and a description of the consequences is very rare. We describe a prisoner who survived after voluntary inhalation of LPG, and who developed ataxia, Parkinsonism, and dystonia. Brain MRI showed bilateral hyperintensity in the basal ganglia and in the cerebellar hemispheres. The clinical evolution and the MRI abnormalities are similar to those described in cases of poisoning by CO where the mechanism of brain injury is related to histotoxic hypoxia. We believe that LPG, considered until now a mixture of gas with low neurotoxic power, may have caused direct toxic damage to the brain, mediated by a mechanism of hypoxia, such as in CO intoxication. Keywords: ataxia, Parkinsonism, dystonia, liquefied petroleum gas

  20. Chlorine gas inhalation: human clinical evidence of toxicity and experience in animal models.

    Science.gov (United States)

    White, Carl W; Martin, James G

    2010-07-01

    Humans can come into contact with chlorine gas during short-term, high-level exposures due to traffic or rail accidents, spills, or other disasters. By contrast, workplace and public (swimming pools, etc.) exposures are more frequently long-term, low-level exposures, occasionally punctuated by unintentional transient increases. Acute exposures can result in symptoms of acute airway obstruction including wheezing, cough, chest tightness, and/or dyspnea. These findings are fairly nonspecific, and might be present after exposures to a number of inhaled chemical irritants. Clinical signs, including hypoxemia, wheezes, rales, and/or abnormal chest radiographs may be present. More severely affected individuals may suffer acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Up to 1% of exposed individuals die. Humidified oxygen and inhaled beta-adrenergic agents are appropriate therapies for victims with respiratory symptoms while assessments are underway. Inhaled bicarbonate and systemic or inhaled glucocorticoids also have been reported anecdotally to be beneficial. Chronic sequelae may include increased airways reactivity, which tends to diminish over time. Airways hyperreactivity may be more of a problem among those survivors that are older, have smoked, and/or have pre-existing chronic lung disease. Individuals suffering from irritant-induced asthma (IIA) due to workplace exposures to chlorine also tend to have similar characteristics, such as airways hyperresponsiveness to methacholine, and to be older and to have smoked. Other workplace studies, however, have indicated that workers exposed to chlorine dioxide/sulfur dioxide have tended to have increased risk for chronic bronchitis and/or recurrent wheezing attacks (one or more episodes) but not asthma, while those exposed to ozone have a greater incidence of asthma. Specific biomarkers for acute and chronic exposures to chlorine gas are currently lacking. Animal models for chlorine gas

  1. Pneumomediastinum from acute inhalation of chlorine gas in 2 young patients.

    Science.gov (United States)

    Li, Baiqiang; Jia, Ling; Shao, Danbing; Liu, Hongmei; Nie, Shinan; Tang, Wenjie; Xu, Baohua; Hu, Zongfeng; Sun, Haichen

    2011-03-01

    Trichloroisocyanuric acid is a high-efficiency and-low toxicity fungicide and bleach. It is commonly used as disinfectant for industrial circulating water, swimming pools, restaurants, and other public places in China. When trichloroisocyanuric acid is put into water, chlorine gas is produced. Chlorine gas is a potent pulmonary irritant that causes acute damage in both the upper and lower respiratory tracts (J Toxicol Clin Toxicol. 1998;36(1-2):87-93). Pneumomediastinum is a rare complication in patients with acute chlorine gas poisoning. A small amount of gas can be asymptomatic, but a large amount of gas entering the mediastinum suddenly will lead to respiratory and circulatory disorder, mediastinal swing, or even cardiopulmonary arrest. Severe chlorine gas poisoning patients usually need mechanical ventilation; if the pneumomediastinum is not found on time, threat to life would be greatly increased. It requires a high index of suspicion for diagnosis and rapid treatment. The proper use of ventilator, timely and effective treatment of original disease, and multiple system organ support had significant impact on the prognosis. The pneumomediastinum case secondary to inhalation of chlorine gas that we report here should remind all emergency department physicians to maintain a high index of suspicion for this disease and seek immediate and proper intervention when treating patients with acute chlorine gas poisoning, once diagnosed, especially in younger patients.

  2. Cerebral and coronary gas embolism from the inhalation of pressurized helium.

    Science.gov (United States)

    Tretjak, Martin; Gorjup, Vojka; Mozina, Hugon; Horvat, Matija; Noc, Marko

    2002-05-01

    Inhalation of helium, which produces a change in the voice, is frequently used among young rock singers to improve their performance. A case report. Adult medical intensive care unit in a university hospital. A 23-yr-old singer, who accidentally inhaled helium from a high pressurized tank without pressure reduction, presented with transient loss of consciousness and chest pain. Electrocardiogram, chest radiograph, biochemical and toxicological analyses, echocardiography, coronary angiography were performed. At admission, the patient slowly regained consciousness. An electrocardiogram showed significant ST elevations in leads I, aVL, and V4-V6. The chest radiograph was consistent with pulmonary congestion and pneumomediastinum. The echocardiogram showed normal sized heart chambers with hypokinesis of the left ventricular lateral wall. Ethanol and urine cannabinoids were present in low concentrations, but no presence of opiates, methadone, cocaine, or amphetamines was documented. Troponin T was positive. Elevation of ST segments gradually disappeared within 30 mins, the drowsiness within 10 hrs, and the thoracic pain within 24 hrs. Coronary angiography showed normal coronary arteries. The patient was discharged on day 3 without any symptoms and with normal electrocardiogram and chest radiograph. Accidental inhalation of helium under high pressure can cause symptomatic cerebral and coronary artery gas embolism.

  3. Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

    Science.gov (United States)

    Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

    2016-12-01

    Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

  4. Odorless inhalant toxic encephalopathy in developing countries household: Gas geyser syndrome

    Directory of Open Access Journals (Sweden)

    Anish Mehta

    2016-01-01

    Full Text Available Background: Liquefied petroleum gas geysers are used very frequently for heating water in developing countries such as India. However, these gas geysers emit various toxic gases; one among them is colorless, odorless carbon monoxide (CO. In the past few years, there were reports of unexplained loss of consciousness in the bathroom. However, the exact cause for these episodes has been recognized as toxic encephalopathy due to toxic gases inhalation mainly CO. Objective: To analyze the clinical profile and outcome of patients brought with loss of consciousness in the bathroom while bathing using gas geyser. Materials and Methods: Case records of patients with the diagnosis of gas geyser syndrome from 2013 to 2015 were retrieved and analyzed. Twenty-four cases were identified and included in the study. This was a retrospective, descriptive study. Results: Twenty-four patients were brought to our Emergency Department with loss of consciousness in the bathroom while bathing. Twenty-one cases had loss of consciousness during bathing and recovered spontaneously. Two cases were found dead in the bathroom and were brought to the Department of Forensic Medicine for postmortem. One case was brought in deep altered state of consciousness and succumbed to illness within 1 week.Conclusion: Awareness regarding CO intoxication due to usage of ill-fitted, ill-ventilated gas geyser is necessary as they are entirely preventable conditions.

  5. [Myocardial infarction in a 16-year old following inhalation of butane gas].

    Science.gov (United States)

    De Naeyer, Ann H R R; de Kort, Sandra W K; Portegies, Mireille C M; Deraedt, Dirk J D L; Buysse, Corinne M P

    2011-01-01

    Butane gas is inhaled by young people with the aim of getting 'high'. This can cause coronary spasm with myocardial infarction and ventricular fibrillation as a result. We report on a 16-year-old male who collapsed at home after sniffing butane. His father, together with a paramedical emergency team that had found ventricular fibrillation, started basic and advanced life support. ECG showed exaggerated ST-elevations and an echocardiography showed a hypokinetic anterior ventricular wall and ventricular septum. After treatment with dobutamine, nitroglycerine, acetylsalicylic acid and dalteparine, the ECG and left ventricular function improved. He was admitted to a pediatric intensive care unit where he was artificially ventilated for 4 days and treated for cardiogenic shock. In the following days his cardiovascular condition improved. Magnetic resonance imaging showed no ischaemic damage of the brain. At 6 weeks his general condition was not as before, but ECG and cardiac function had almost recovered. Young people who experiment with inhalation of volatile substances generally do not know how dangerous this is. Provision of information about the possible consequences will have a preventive effect.

  6. A mouse model for in vivo tracking of the major dust mite allergen Der p 2 after inhalation.

    Science.gov (United States)

    Johansson, Linda; Svensson, Linda; Bergström, Ulrika; Jacobsson-Ekman, Gunilla; Arnér, Elias S J; van Hage, Marianne; Bucht, Anders; Gafvelin, Guro

    2005-07-01

    Inhaled environmental antigens, i.e. allergens, cause allergic symptoms in millions of patients worldwide. As little is known about the fate of an allergen upon inhalation, we addressed this issue for a major dust mite allergen, Der p 2. First, a model for Der p 2-sensitization was established in C57BL/6 J mice, in which sensitized mice mounted a Der p 2-specific IgE-response with eosinophilic lung inflammation after allergen challenge in the airways. In this model, we applied recombinant Der p 2 carrying a novel C-terminal tetrapeptide Sel-tag enabling labelling with the gamma-emitting radionuclide 75Se at a single selenocysteine residue ([75Se]Der p 2). In vivo tracking of intratracheally administered [75Se]Der p 2 using whole-body autoradiography revealed that [75Se]Der p 2-derived radioactivity persisted in the lungs of sensitized mice as long as 48 h. Radioactivity was also detected in kidneys, liver and in enlarged lung-associated lymph nodes. Interestingly, a larger proportion of radioactivity was found in the lungs of sensitized compared with nonsensitized mice 24 h after intratracheal instillation of [75Se]Der p 2. A radioactive protein corresponding to intact Der p 2 could only be detected in the lungs, whereas [75Se]Der p 2-derived radioactivity was recovered in known selenoproteins both in lung and other organs. Hence, using the recently developed Sel-tag method in a mouse model for Der p 2-sensitization, we could track the fate of an inhaled allergen in vivo. Based upon our findings, we conclude that the inflammatory state of the lung influences the rate of metabolism and clearance of Der p 2. Thus, an allergic response to the inhaled allergen may lead to prolonged retention of Der p 2 in the lung.

  7. Hemodynamics and Gas Exchange Effects of Inhaled Nitrous Oxide in Patients with Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2006-01-01

    Full Text Available Inhaled nitrous oxide (iNO therapy aimed at improving pulmonary oxygenizing function and at decreasing artificial ventilation (AV load has been used in foreign clinical practice in the past decade. The study was undertaken to evaluate the hemodynamic and gas exchange effects of iNO in acute respiratory distress syndrome (ARDS that developed after car-diosurgical operations. Fifty-eight (43 males and 15 females patients aged 21 to 76 (55.2±2.4 years were examined. The study has demonstrated that in 48.3% of cases, the early stage of ARDS is attended by the increased tone pulmonary vessels due to impaired NO-dependent vasodilatation. In these patients, iNO therapy is an effective therapeutic method for correcting hemodynamic disorders and lung oxygenizing function.

  8. In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients.

    Science.gov (United States)

    Hussein, Raghda R S; M A Ali, Ahmed; Salem, Heba F; Abdelrahman, Maha M; Said, Amira S A; Abdelrahim, Mohamed E A

    2017-11-01

    Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

  9. The effect of a heat and moisture exchanger on gas flow in a Mapleson F breathing system during inhalational induction.

    Science.gov (United States)

    Da Fonseca, J M; Wheeler, D W; Pook, J A

    2000-06-01

    Heat and moisture exchangers (HMEs) humidify, warm and filter inspired gas, protecting patients and apparatus during anaesthesia. Their incorporation into paediatric anaesthetic breathing systems is recommended. We experienced delays in inhalational induction whilst using a Mapleson F breathing system with an HME. We have demonstrated that the HME significantly alters gas flow within the breathing system. Approximately half of the fresh gas flow is delivered to the patient, the remainder being wasted into the expiratory limb of the breathing system. We suggest that the HME should be removed from the Mapleson F breathing system until inhalational induction is complete, or that the reservoir bag is completely occluded until an effective seal is obtained with the mask.

  10. Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

    Science.gov (United States)

    Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

    2014-11-01

    To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

  11. Inhalation pressure distributions for medical gas mixtures calculated in an infant airway morphology model.

    Science.gov (United States)

    Gouinaud, Laure; Katz, Ira; Martin, Andrew; Hazebroucq, Jean; Texereau, Joëlle; Caillibotte, Georges

    2015-01-01

    A numerical pressure loss model previously used for adult human airways has been modified to simulate the inhalation pressure distribution in a healthy 9-month-old infant lung morphology model. Pressure distributions are calculated for air as well as helium and xenon mixtures with oxygen to investigate the effects of gas density and viscosity variations for this age group. The results indicate that there are significant pressure losses in infant extrathoracic airways due to inertial effects leading to much higher pressures to drive nominal flows in the infant airway model than for an adult airway model. For example, the pressure drop through the nasopharynx model of the infant is much greater than that for the nasopharynx model of the adult; that is, for the adult-versus-child the pressure differences are 0.08 cm H2O versus 0.4 cm H2O, 0.16 cm H2O versus 1.9 cm H2O and 0.4 cm H2O versus 7.7 cm H2O, breathing helium-oxygen (78/22%), nitrogen-oxygen (78/22%) and xenon-oxygen (60/40%), respectively. Within the healthy lung, viscous losses are of the same order for the three gas mixtures, so the differences in pressure distribution are relatively small.

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

    Directory of Open Access Journals (Sweden)

    Jana Dumkova

    2016-06-01

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

  13. Protein Crystallography under Xenon and Nitrous Oxide Pressure: Comparison with In Vivo Pharmacology Studies and Implications for the Mechanism of Inhaled Anesthetic Action

    Science.gov (United States)

    Colloc'h, Nathalie; Sopkova-de Oliveira Santos, Jana; Retailleau, Pascal; Vivarès, Denis; Bonneté, Françoise; Langlois d'Estainto, Béatrice; Gallois, Bernard; Brisson, Alain; Risso, Jean-Jacques; Lemaire, Marc; Prangé, Thierry; Abraini, Jacques H.

    2007-01-01

    In contrast with most inhalational anesthetics, the anesthetic gases xenon (Xe) and nitrous oxide (N2O) act by blocking the N-methyl-d-aspartate (NMDA) receptor. Using x-ray crystallography, we examined the binding characteristics of these two gases on two soluble proteins as structural models: urate oxidase, which is a prototype of a variety of intracellular globular proteins, and annexin V, which has structural and functional characteristics that allow it to be considered as a prototype for the NMDA receptor. The structure of these proteins complexed with Xe and N2O were determined. One N2O molecule or one Xe atom binds to the same main site in both proteins. A second subsite is observed for N2O in each case. The gas-binding sites are always hydrophobic flexible cavities buried within the monomer. Comparison of the effects of Xe and N2O on urate oxidase and annexin V reveals an interesting relationship with the in vivo pharmacological effects of these gases, the ratio of the gas-binding sites' volume expansion and the ratio of the narcotic potency being similar. Given these data, we propose that alterations of cytosolic globular protein functions by general anesthetics would be responsible for the early stages of anesthesia such as amnesia and hypnosis and that additional alterations of ion-channel membrane receptor functions are required for deeper effects that progress to “surgical” anesthesia. PMID:17028130

  14. Gas transport during in vitro and in vivo preclinical testing of inert gas therapies

    Directory of Open Access Journals (Sweden)

    Ira Katz

    2016-01-01

    Full Text Available New gas therapies using inert gases such as xenon and argon are being studied, which require in vitro and in vivo preclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze an in vitro experiment for gas transport to a 96 cell well plate and an in vivo delivery to a small animal chamber, where the key processes considered are the wash-in of test gas into an apparatus dead volume, the diffusion of test gas through the liquid media in a well of a cell test plate, and the pharmacokinetics in a rat. In the case of small animals in a chamber, the key variable controlling the kinetics is the chamber wash-in time constant that is a function of the chamber volume and the gas flow rate. For cells covered by a liquid media the diffusion of gas through the liquid media is the dominant mechanism, such that liquid depth and the gas diffusion constant are the key parameters. The key message from these analyses is that the transport of gas during preclinical experiments can be important in determining the true dose as experienced at the site of action in an animal or to a cell.

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

    Science.gov (United States)

    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

  16. [Atypical case of teenager fatal poisoning by butane as a result of gas for lighters inhalation against his will].

    Science.gov (United States)

    Celiński, Rafał; Skowronek, Rafał; Uttecht-Pudełko, Anna

    2013-01-01

    Inhalatomania with volatile organic compounds is a still present phenomenon among Polish young adolescents. Conscious, voluntary exposition on such substances may result in serious health consequences, including sudden death in the course of acute intoxication. In this paper, atypical case of death of 16-year-old teenager as a result of complications of physically forced inhalation of gas for lighters is presented. According to testimonies of witnesses, the container was placed in the mouth of victim and the gas was introduced directly to his throat. Autopsy revealed small damage of tooth with corresponding bruising of lower lip; brain and lung oedma; single bruisings in the upper respiratory tract and subpleural. Chemical-toxicological analysis of blood, brain and lung samples taken during autopsy revealed in all of them the presence of n-butan--a component of gas for lighters (the greatest in brain and lung tissues). Additionally, in blood the presence of carboxyhemoglobin (COHb) in concentration 7% was confirmed. Based on the results of analyses, acute intoxication with n-butan was estimated as a cause of death; however the key role played the information obtained during the investigation. This case shows, that deaths resulting from gas for lighters inhalation may be a consequence of forced exposition--against victim's will. So medical staff should always check, if on the body of patient there are any signs of physical constraint (the presence of bruisings in the area of viscerocranium and oral cavity, teeth damages, etc.).

  17. In Vitro and In Vivo Performance of Novel Spray Dried Andrographolide Loaded Scleroglucan Based Formulation for Dry Powder Inhaler.

    Science.gov (United States)

    Mali, Ashwin Jagannath; Bothiraja, Chellampillai; Purohit, Ravindra Nandlal; Pawar, Atmaram Pandurang

    2017-01-01

    Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity. The SDAGP formulation was evaluated for physicochemical properties and in vitro/in vivo lung deposition. Further, antihypertensive activity was studied by monocrotaline (MCT) induced rat model. The SDAGP exhibited mean median aerodynamic diameter (MMAD) and fine particle fraction (FPF) of 3.37 ± 0.47 µm and 60.24 ± 0.98%. The in vivo absorption profile of final formulation reflected increased lung deposition of AGP at the end of 24 h with no signs of inflammation and toxicity. Moreover, SDAGP formulation confirmed enhanced antihypertensive activity. The results proved use of AGP and SCLG as a novel bioactive and carrier with enhanced lung deposition and pulmonary antihypertensive activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. A method for determining an indicator of effective dose calculation due to inhalation of Radon and its progeny from in vivo measurements

    CERN Document Server

    Estrada, J

    1994-01-01

    Direct measurement of the absolved dose to lung tissue from inhalation of radon and its progeny is not possible and must be calculated using dosimetric models, taking into consideration the several parameters upon which the dose calculation depends. To asses the dose due to inhalation of radon and its progeny, it is necessary to estimate the cumulative exposure. Historically, this has been done using WLM values estimated with measurements of radon concentration in air. The radon concentration in air varies significantly, however, in space with time, and the exposed individual is also constantly moving around. This makes it almost impossible to obtain a precise estimate of an individual's inhalation exposure. This work describes a pilot study to calculate lung dose from the deposition of radon progeny, via estimates of cumulative exposure derived from in vivo measurements of sup 2 sup 1 sup 0 Pb, in subjects exposed to above-average radon and its progeny concentrations in their home environments. The measureme...

  19. Effect of N-acetylcysteine on gas exchange after methacholine challenge and isoprenaline inhalation in the dog.

    Science.gov (United States)

    Ueno, O; Lee, L N; Wagner, P D

    1989-03-01

    N-acetylcysteine (NAC) has antioxidant and possibly mucolytic properties. To determine whether NAC could be of benefit in acute bronchoconstriction induced by methacholine, 12 of 24 anaesthetized dogs (group 1) received NAC i.v. (loading dose 150 mg.kg-1, then 20 mg.kg-1.hr-1). The other 12 (group 2) received diluent. Nebulized methacholine (1%) was then inhaled until arterial oxygen tension (PaO2) fell to a mean of 5.5 kPa, after which isoprenaline 0.5% was inhaled in six dogs of each group to reverse bronchoconstriction. Over the next 3 h we measured total lung resistance, functional residual capacity (FRC), haemodynamic variables, and pulmonary gas exchange for respiratory and inert gases. After methacholine challenge, lung resistance increased and then fell similarly for both groups, but PaO2 was higher in the NAC group (by 0.6-1.9 kPa) throughout the observation period. The ventilation-perfusion distribution measured by inert gas elimination also showed less abnormality in the NAC treated dogs over this time. Mucus was visible during post-mortem in the large airways in about half of the dogs in both groups, with no significant differences between them. These results show that NAC produces a measurable improvement in gas exchange following methacholine challenge (both with and without subsequent isoprenaline therapy) by mechanisms that remain to be determined.

  20. A method for calculating the gas volume proportions and inhalation temperature of inert gas mixtures allowing reaching normothermic or hypothermic target body temperature in the awake rat

    Directory of Open Access Journals (Sweden)

    Jacques H Abraini

    2017-01-01

    Full Text Available The noble gases xenon (Xe and helium (He are known to possess neuroprotective properties. Xe is considered the golden standard neuroprotective gas. However, Xe has a higher molecular weight and lower thermal conductivity and specific heat than those of nitrogen, the main diluent of oxygen (O2 in air, conditions that could impair or at least reduce the intrinsic neuroprotective properties of Xe by increasing the critical care patient's respiratory workload and body temperature. In contrast, He has a lower molecular weight and higher thermal conductivity and specific heat than those of nitrogen, but is unfortunately far less potent than Xe at providing neuroprotection. Therefore, combining Xe with He could allow obtaining, depending on the gas inhalation temperature and composition, gas mixtures with neutral or hypothermic properties, the latter being advantageous in term of neuroprotection. However, calculating the thermal properties of a mixture, whatever the substances – gases, metals, rubbers, etc. – is not trivial. To answer this question, we provide a graphical method to assess the volume proportions of Xe, He and O2 that a gas mixture should contain, and the inhalation temperature to which it should be administered to allow a clinician to maintain the patient at a target body temperature.

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

    Science.gov (United States)

    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.

  2. Differentiation at necropsy between in vivo gas embolism and putrefaction using a gas score.

    Science.gov (United States)

    Bernaldo de Quirós, Yara; Saavedra, Pedro; Møllerløkken, Andreas; Brubakk, Alf O; Jørgensen, Arve; González-Díaz, Oscar; Martín-Barrasa, Jose L; Fernández, Antonio

    2016-06-01

    Gas bubble lesions consistent with decompression sickness in marine mammals were described for the first time in beaked whales stranded in temporal and spatial association with military exercises. Putrefaction gas is a post-mortem artifact, which hinders the interpretation of gas found at necropsy. Gas analyses have been proven to help differentiating putrefaction gases from gases formed after hyperbaric exposures. Unfortunately, chemical analysis cannot always be performed. Post-mortem computed tomography is used to study gas collections, but many different logistical obstacles and obvious challenges, like the size of the animal or the transport of the animal from the stranding location to the scanner, limit its use in stranded marine mammals. In this study, we tested the diagnostic value of an index-based method for characterizing the amount and topography of gas found grossly during necropsies. For this purpose, putrefaction gases, intravenously infused atmospheric air, and gases produced by decompression were evaluated at necropsy with increased post-mortem time in New Zealand White Rabbits using a gas score index. Statistical differences (P<0.001) were found between the three experimental models immediately after death. Differences in gas score between in vivo gas embolism and putrefaction gases were found significant (P<0.05) throughout the 67h post-mortem. The gas score-index is a new and simple method that can be used by all stranding networks, which has been shown through this study to be a valid diagnostic tool to distinguish between fatal decompression, iatrogenic air embolism and putrefaction gases at autopsies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Differentiation at autopsy between in vivo gas embolism and putrefaction using gas composition analysis.

    Science.gov (United States)

    Bernaldo de Quirós, Yara; González-Díaz, Oscar; Møllerløkken, Andreas; Brubakk, Alf O; Hjelde, Astrid; Saavedra, Pedro; Fernández, Antonio

    2013-03-01

    Gas embolism can arise from different causes (iatrogenic accidents, criminal interventions, or diving related accidents). Gas analyses have been shown to be a valid technique to differentiate between putrefaction gases and gas embolism. In this study, we performed systematic necropsies at different postmortem times in three experimental New Zealand White Rabbits models: control or putrefaction, infused air embolism, and compression/decompression. The purpose of this study was to look for qualitative and quantitative differences among groups and to observe how putrefaction gases mask in vivo gas embolism. We found that the infused air embolism and compression/decompression models had a similar gas composition prior to 27-h postmortem, being typically composed of around 70-80 % of N(2) and 20-30 % of CO(2), although unexpected higher CO(2) concentrations were found in some decompressed animals, putting in question the role of CO(2) in decompression. All these samples were statistically and significantly different from more decomposed samples. Gas composition of samples from more decomposed animals and from the putrefaction model presented hydrogen, which was therefore considered as a putrefaction marker.

  4. Inhaled Steroids

    Science.gov (United States)

    ... Medications Long-Term Control Medications Inhaled Steroids Inhaled Steroids Make an Appointment Ask a Question Refer Patient ... more about steroids? What are some common inhaled steroids? Common inhaled steroids include: Asmanex ® (mometasone) Alvesco ® (ciclesonide) ...

  5. Biodegradability of inhaled para-aramid respirable-sized fiber-shaped particulates: mechanistic in vivo and in vitro studies.

    Science.gov (United States)

    Warheit, D B; Hartsky, M A; Reed, K L; Webb, T R

    2001-07-01

    Biopersistence represents an important health-related issue in fiber toxicology. These studies were undertaken to elucidate the mechanism(s) through which inhaled p-aramid respirable-sized fiber-shaped particulates (RFP) are biodegraded in the lungs of exposed rats and hamsters. Previously, we and others have reported that, following deposition in the lung, long p-aramid RFPs are cleaved into shorter fibrous fragments. To investigate the mechanisms of RFP biodegradation, we have postulated that lung fluids coat/activate p-aramid RFP following deposition in the alveolar regions of the lung, thus predisposing the RFP to enzymatic attack and consequent shortening. This process enhances the rate of clearance of the inhaled RFP. To test this hypothesis, we have conducted both in vivo and in vitro cellular and noncellular investigations. First, p-aramid or cellulose RFP were instilled into the lungs of rats and the lungs were digested 24 h postexposure using two different digestion techniques: (1) a conventional ethanolic KOH method and (2) an enzymatic method that simulates the action of lung enzymes. Cellulose RFP were utilized as a control organic fiber-type that is known to be biopersistent. The results demonstrated that the enzymatic but not the KOH method resulted in transverse cleavage of the p-aramid RFP; the lengths of cellulose RFP recovered from rat lungs were not reduced by either method. Next, standardized preparations of p-aramid RFP or cellulose RFP were incubated with saline or lung fluids and then processed by one of two tissue digestion techniques. Mean lengths of p-aramid RFP incubated with saline and processed with KOH or the enzyme method were not found to be altered. Indeed, only the preparation of p-aramid RFP that had been incubated with bronchoalveolar lavage (BAL) fluids and processed with the enzyme solution resulted in cleavage of p-aramid RFP. Moreover, when the BAL fluids were autoclaved to denature proteins, the length dimensions of p

  6. Influence of inhaled nitric oxide on gas exchange during normoxic and hypoxic exercise in highly trained cyclists.

    Science.gov (United States)

    Sheel, A W; Edwards, M R; Hunte, G S; McKenzie, D C

    2001-03-01

    This study tested the effects of inhaled nitric oxide [NO; 20 parts per million (ppm)] during normoxic and hypoxic (fraction of inspired O(2) = 14%) exercise on gas exchange in athletes with exercise-induced hypoxemia. Trained male cyclists (n = 7) performed two cycle tests to exhaustion to determine maximal O(2) consumption (VO(2 max)) and arterial oxyhemoglobin saturation (Sa(O(2)), Ohmeda Biox ear oximeter) under normoxic (VO(2 max) = 4.88 +/- 0.43 l/min and Sa(O(2)) = 90.2 +/- 0.9, means +/- SD) and hypoxic (VO(2 max) = 4.24 +/- 0.49 l/min and Sa(O(2)) = 75.5 +/- 4.5) conditions. On a third occasion, subjects performed four 5-min cycle tests, each separated by 1 h at their respective VO(2 max), under randomly assigned conditions: normoxia (N), normoxia + NO (N/NO), hypoxia (H), and hypoxia + NO (H/NO). Gas exchange, heart rate, and metabolic parameters were determined during each condition. Arterial blood was drawn at rest and at each minute of the 5-min test. Arterial PO(2) (Pa(O(2))), arterial PCO(2), and Sa(O(2)) were determined, and the alveolar-arterial difference for PO(2) (A-aDO(2)) was calculated. Measurements of Pa(O(2)) and Sa(O(2)) were significantly lower and A-aDO(2) was widened during exercise compared with rest for all conditions (P 0.05). We conclude that inhalation of 20 ppm NO during normoxic and hypoxic exercise has no effect on gas exchange in highly trained cyclists.

  7. Loss of Basal Cells Precedes Bronchiolitis Obliterans–Like Pathological Changes in a Murine Model of Chlorine Gas Inhalation

    Science.gov (United States)

    O’Koren, Emily G.; Hogan, Brigid L. M.

    2013-01-01

    Bronchiolitis obliterans (BO) is a major cause of chronic airway dysfunction after toxic chemical inhalation. The pathophysiology of BO is not well understood, but epithelial cell injury has been closely associated with the development of fibrotic lesions in human studies and in animal models of both toxin-induced and transplant-induced BO. However, whereas almost all cases and models of BO include epithelial injury, not all instances of epithelial injury result in BO, suggesting that epithelial damage per se is not the critical event leading to the development of BO. Here, we describe a model of chlorine-induced BO in which mice develop tracheal and large airway obliterative lesions within 10 days of exposure to high (350 parts per million [ppm]), but not low (200 ppm), concentrations of chlorine gas. Importantly, these lesions arise only under conditions and in areas in which basal cells, the resident progenitor cells for large airway epithelium, are eliminated by chlorine exposure. In areas of basal cell loss, epithelial regeneration does not occur, resulting in persistent regions of epithelial denudation. Obliterative airway lesions arise specifically from regions of epithelial denudation in a process that includes inflammatory cell infiltration by Day 2 after exposure, fibroblast infiltration and collagen deposition by Day 5, and the ingrowth of blood vessels by Day 7, ultimately leading to lethal airway obstruction by Days 9–12. We conclude that the loss of epithelial progenitor cells constitutes a critical factor leading to the development of obliterative airway lesions after chemical inhalation. PMID:23742075

  8. Loss of basal cells precedes bronchiolitis obliterans-like pathological changes in a murine model of chlorine gas inhalation.

    Science.gov (United States)

    O'Koren, Emily G; Hogan, Brigid L M; Gunn, Michael Dee

    2013-11-01

    Bronchiolitis obliterans (BO) is a major cause of chronic airway dysfunction after toxic chemical inhalation. The pathophysiology of BO is not well understood, but epithelial cell injury has been closely associated with the development of fibrotic lesions in human studies and in animal models of both toxin-induced and transplant-induced BO. However, whereas almost all cases and models of BO include epithelial injury, not all instances of epithelial injury result in BO, suggesting that epithelial damage per se is not the critical event leading to the development of BO. Here, we describe a model of chlorine-induced BO in which mice develop tracheal and large airway obliterative lesions within 10 days of exposure to high (350 parts per million [ppm]), but not low (200 ppm), concentrations of chlorine gas. Importantly, these lesions arise only under conditions and in areas in which basal cells, the resident progenitor cells for large airway epithelium, are eliminated by chlorine exposure. In areas of basal cell loss, epithelial regeneration does not occur, resulting in persistent regions of epithelial denudation. Obliterative airway lesions arise specifically from regions of epithelial denudation in a process that includes inflammatory cell infiltration by Day 2 after exposure, fibroblast infiltration and collagen deposition by Day 5, and the ingrowth of blood vessels by Day 7, ultimately leading to lethal airway obstruction by Days 9-12. We conclude that the loss of epithelial progenitor cells constitutes a critical factor leading to the development of obliterative airway lesions after chemical inhalation.

  9. A HYBRID CFD-PBPK MODEL OF INHALED CHLORINE GAS UPTAKE AND TISSUE DOSIMETRY IN THE ISOLATED UPPER RESPIRATORY TRACT (URT) OF F344 RATS

    Science.gov (United States)

    Chlorine (Cl2), an important commercial gas, is highly reactive in water, causing irritant effects in the respiratory tract on inhalation. Nasal extraction of Cl2 is high and resultant lesions in the respiratory tract show a proximal to distal distribution ...

  10. Six-month low level chlorine dioxide gas inhalation toxicity study with two-week recovery period in rats

    Directory of Open Access Journals (Sweden)

    Akamatsu Akinori

    2012-02-01

    Full Text Available Abstract Background Chlorine dioxide (CD gas has a potent antimicrobial activity at extremely low concentration and may serve as a new tool for infection control occupationally as well as publicly. However, it remains unknown whether the chronic exposure of CD gas concentration effective against microbes is safe. Therefore, long-term, low concentration CD gas inhalation toxicity was studied in rats as a six-month continuous whole-body exposure followed by a two-week recovery period, so as to prove that the CD gas exposed up to 0.1 ppm (volume ratio is judged as safe on the basis of a battery of toxicological examinations. Methods CD gas at 0.05 ppm or 0.1 ppm for 24 hours/day and 7 days/week was exposed to rats for 6 months under an unrestrained condition with free access to chow and water in a chamber so as to simulate the ordinary lifestyle in human. The control animals were exposed to air only. During the study period, the body weight as well as the food and water consumptions were recorded. After the 6-month exposure and the 2-week recovery period, animals were sacrificed and a battery of toxicological examinations, including biochemistry, hematology, necropsy, organ weights and histopathology, were performed. Results Well regulated levels of CD gas were exposed throughout the chamber over the entire study period. No CD gas-related toxicity sign was observed during the whole study period. No significant difference was observed in body weight gain, food and water consumptions, and relative organ weight. In biochemistry and hematology examinations, changes did not appear to be related to CD gas toxicity. In necropsy and histopathology, no CD gas-related toxicity was observed even in expected target respiratory organs. Conclusions CD gas up to 0.1 ppm, exceeding the level effective against microbes, exposed to whole body in rats continuously for six months was not toxic, under a condition simulating the conventional lifestyle in human.

  11. The hydrogen gas clearance method for liver blood flow examination: inhalation or local application of hydrogen?

    Science.gov (United States)

    Metzger, H P

    1989-01-01

    The combined method of hydrogen inhalation and local hydrogen production enable the determination of hepatic blood flow (HBF) and local hepatic blood flow (LHBF). LHBF was registered within a small superficial tissue volume of 0.5 mm in diameter by means of a multi-wire electrode having 200 microns producing and 100 microns measuring wires arranged within less than 300 microns distance between the measuring wires. The feeding current for hydrogen production was 1 microA, the potential less than 10 V. The clearance in response to inhalation was registered by means of the same measuring electrodes within the same tissue volume. Spontaneously breathing rats (Wistar-Frömter strain, 180-230 g bw, N = 19, ketamin-xylazine anesthesia, artificial respiration) showed the following flow values: HBF +/- SD = 0.50 +/- 0.26 ml/g.min, n = 48 registrations; LHBF +/- SD = 4.66 +/- 2.13 ml/g.min, n = 43. The validity of the combined method is demonstrated in the LHBF/HBF graph which summarizes the data of hemorrhagic and control animals, m = 0.1 and yo = 0.001. The correlation coefficient of r = 0.685 shows a reasonable correlation of the combined data despite the wide scattering of the individual values.

  12. Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação de desempenho de pulmões submetidos à administração de prostaciclina inalada versus parenteral An experimental rat model of ex vivo lung perfusion for the assessment of lungs after prostacyclin administration: inhaled versus parenteral routes

    Directory of Open Access Journals (Sweden)

    Paulo Francisco Guerreiro Cardoso

    2011-10-01

    storage at 4ºC for 6 h. The heart-lung blocks were then ventilated and perfused in an ex vivo lung perfusion system for 50 min. Respiratory mechanics, hemodynamics, and gas exchange were assessed. RESULTS: Mean pulmonary artery pressure following nebulization decreased in all groups (p < 0.001, with no significant differences among the groups. During the ex vivo perfusion, respiratory mechanics did not differ among the groups, although relative oxygenation capacity decreased significantly in the IS and PS groups (p = 0.04, whereas mean pulmonary artery pressure increased significantly in the IS group. CONCLUSIONS: The experimental model of inhaled PGI2 administration during lung extraction is feasible and reliable. During reperfusion, hemodynamics and gas exchange trended toward better performance with the use of PGI2 than that with the use of saline.

  13. Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury.

    Science.gov (United States)

    Aggarwal, Saurabh; Lam, Adam; Bolisetty, Subhashini; Carlisle, Matthew A; Traylor, Amie; Agarwal, Anupam; Matalon, Sadis

    2016-01-10

    Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme-dependent oxidative injury underlies the pathogenesis of Br2 toxicity. C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 μg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1-/-) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. This is the first study delineating the role of heme in ALI caused by Br2. The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI.

  14. Surface Energy Determined by Inverse Gas Chromatography as a Tool to Investigate Particulate Interactions in Dry Powder Inhalers.

    Science.gov (United States)

    Das, Shyamal C; Tucker, Ian G; Stewart, Peter J

    2015-01-01

    Dry powder inhalers (DPIs) usually contain drug particles <6 µm which agglomerate and/ or adhere on the surfaces of large carriers particles. The detachment of drug particles from carriers and de-agglomeration of drug particles into primary particles is essential for drug deposition in the deep lung. These processes are influenced by the surface energy of particles. Inverse gas chromatography (IGC) has been used to determine the surface energy of powder particles used in DPI to characterize materials and to understand aerosolization behaviour. Early studies used an infinite dilution technique to determine nonpolar surface energy and free energy of adsorption for polar interactions separately. Although some correlations were observed with the change in nonpolar surface energy before and after micronization, milling and storage, a lack of consistency in the change of free energy of adsorption was common. Moreover, a consistent relationship between complex de-agglomeration behaviour and surface energy has not been established and there are even some examples of negative correlation. In fact, nonpolar surface energy at infinite dilution is an incomplete representation of powder surface characteristics. The techniques for measuring polar surface energy, total surface energy and surface energy distribution have provided more revealing information about surface energetics of powders. Surface energy distributions determined by IGC or surface energy analyser have been successfully used to understand energetic heterogeneity of surfaces, characterize different polymorphs and understand changes due to micronization, structural relaxation, dry coating and storage. Efforts have been made to utilize surface energy distribution data to calculate powder strength distribution and to explain complex de-agglomeration behaviour of DPI formulations.

  15. MODULAR APPLICATION OF COMPUTATIONAL MODELS OF INHALED REACTIVE GAS DOSIMETRY FOR RISK ASSESSMENT OF RESPIRATORY TRACT TOXICITY: CHLORINE

    Science.gov (United States)

    Inhaled reactive gases typically cause respiratory tract toxicity with a prominent proximal to distal lesion pattern. This pattern is largely driven by airflow and interspecies differences between rodents and humans result from factors such as airway architecture, ventilation ra...

  16. Effects of different fresh gas flows with or without a heat and moisture exchanger on inhaled gas humidity in adults undergoing general anaesthesia: A systematic review and meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Braz, José R C; Braz, Mariana G; Hayashi, Yoko; Martins, Regina H G; Betini, Marluci; Braz, Leandro G; El Dib, Regina

    2017-08-01

    The minimum inhaled gas absolute humidity level is 20 mgH2O l for short-duration use in general anaesthesia and 30 mgH2O l for long-duration use in intensive care to avoid respiratory tract dehydration. The aim is to compare the effects of different fresh gas flows (FGFs) through a circle rebreathing system with or without a heat and moisture exchanger (HME) on inhaled gas absolute humidity in adults undergoing general anaesthesia. Systematic review and meta-analyses of randomised controlled trials. We defined FGF (l min) as minimal (0.25 to 0.5), low (0.6 to 1.0) or high (≥2). We extracted the inhaled gas absolute humidity data at 60 and 120 min after connection of the patient to the breathing circuit. The effect size is expressed as the mean differences and corresponding 95% confidence intervals (CI). PubMed, EMBASE, SciELO, LILACS and CENTRAL until January 2017. We included 10 studies. The inhaled gas absolute humidity was higher with minimal flow compared with low flow at 120 min [mean differences 2.51 (95%CI: 0.32 to 4.70); P = 0.02] but not at 60 min [mean differences 2.95 (95%CI: -0.95 to 6.84); P = 0.14], and higher with low flow compared with high flow at 120 min [mean differences 7.19 (95%CI: 4.53 to 9.86); P < 0.001]. An inhaled gas absolute humidity minimum of 20 mgH2O l was attained with minimal flow at all times but not with low or high flows. An HME increased the inhaled gas absolute humidity: with minimal flow at 120 min [mean differences 8.49 (95%CI: 1.15 to 15.84); P = 0.02]; with low flow at 60 min [mean differences 9.87 (95%CI: 3.18 to 16.57); P = 0.04] and 120 min [mean differences 7.19 (95%CI: 3.29 to 11.10); P = 0.003]; and with high flow of 2 l min at 60 min [mean differences 6.46 (95%CI: 4.05 to 8.86); P < 0.001] and of 3 l min at 120 min [mean differences 12.18 (95%CI: 6.89 to 17.47); P < 0.001]. The inhaled gas absolute humidity data attained or were near 30 mgH2O l when an

  17. Evaluation of oleoresin capsicum of Capsicum frutescenes var. Nagahari containing various percentages of capsaicinoids following inhalation as an active ingredient for tear gas munitions.

    Science.gov (United States)

    Kumar, Pravin; Deb, Utsab; Kaushik, M P

    2012-08-01

    Comparative efficacy as peripheral sensory irritant, oral and inhalation exposure studies were carried out on oleoresin capsicum (OC) of Capsicum frutescence var. Nagahari containing various percentages of capsaicinoids and two synthetic isomers of capsaicin in Swiss albino male mouse model to come up with a suitable active ingredient from natural source for tear gas munitions. The compounds screened were OC having varying percentages of capsaicinoids (20, 40 and 80%, respectively) and synthetic isomers (E and Z) of capsaicin (8-methyl-N-vanillyl-6-nonenamide). Mice were exposed to pyrotechnically generated smoke of the compounds in an all glass static exposure chamber for 15 min to determine acute inhalation toxicity (LC₅₀) and quantitative sensory irritation potential (RD₅₀). Acute oral median lethal dose (LD₅₀) was also evaluated. Safety index of tear gas (SITG), a ratio of lethal concentration 50% (LC₅₀) and the concentration which depresses respiration by 50% (RD₅₀) due to peripheral sensory irritation is also proposed. The compound having highest SITG is considered as the most suitable to be used for tear gas munitions. The study revealed that oleoresin capsicum containing 40% capsaicinoids had the highest SITG among the compounds studied. The oral dosage versus mortality pattern of some compounds did not follow a true dose-response curve (DRC); however, following inhalation, all the compounds followed DRC. It was concluded that oleoresin capsicum (40% capsaicinoids) may be considered as the most suitable and environmental friendly compound from natural source to be used as an active ingredient for tear gas munitions.

  18. Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human skin in vivo.

    NARCIS (Netherlands)

    Moeskops, B.W.M.; Steeghs, M.M.L.; Swam, K. van; Cristescu, S.M.; Scheepers, P.T.J.; Harren, F.J.M.

    2006-01-01

    Trace gases emitted by human skin in vivo are monitored non-invasively and in real time using laser-based photoacoustic detection and proton-transfer reaction mass spectrometry. A small quartz cuvette is placed on the skin to create a headspace from which a carrier gas transports the skin emissions

  19. Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

    Directory of Open Access Journals (Sweden)

    Ballesteros KA

    2012-11-01

    Full Text Available Kristen A Ballesteros,1 Angela Sikorski,2 James E Orfila,3 Joe L Martinez Jr41Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA; 2Texas A&M University Texarkana, Texarkana, TX, USA; 3University of Colorado in Denver, Denver, CO, USA; 4University of Illinois in Chicago, Chicago, IL, USAAbstract: Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3. We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3 to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA, or 3-[(R-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP. Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals

  20. Inhalation Injuries

    Science.gov (United States)

    Inhalation injuries are acute injuries to your respiratory system and lungs. They can happen if you breathe in toxic substances, such as smoke (from fires), chemicals, particle pollution, and gases. Inhalation injuries can also be caused by extreme heat; these are a type of thermal injuries. ...

  1. Nicotine Oral Inhalation

    Science.gov (United States)

    Nicotine oral inhalation is used to help people stop smoking. Nicotine oral inhalation should be used together with a smoking ... Nicotine oral inhalation comes as a cartridge to inhale by mouth using a special inhaler. Follow the directions on ...

  2. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

    Science.gov (United States)

    Kawamura, Tomohiro; Wakabayashi, Nobunao; Shigemura, Norihisa; Huang, Chien-Sheng; Masutani, Kosuke; Tanaka, Yugo; Noda, Kentaro; Peng, Ximei; Takahashi, Toru; Billiar, Timothy R.; Okumura, Meinoshin; Toyoda, Yoshiya; Kensler, Thomas W.

    2013-01-01

    Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen. PMID:23475767

  3. The effect of vehicles on spray drying of rifampicin inhalable microparticles: In vitro and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Backgrond and the purpose of the study: The aim of this study was to evaluate the effect of solvents used in the spray drying and the aerodynamic properties of the rifampicin microparticles and pulmonary absorption of the microparticles. Methods: Different mixtures of dichloromethane and water were used as solvents for spray drying of rifampicin microparticles. The water to dichloromethane ratios were 25:75, 50:50, 75:25, 80:20, 90:10 and 100:0.   The solutions were dried at inlet temperature of 70 °C. The powder properties of the samples were examined by laser diffraction, scanning electron microscopy (SEM, helium densitometer and infrared spectroscopy (IR. The aerosolization performance of these formulations was investigated using an Andersen cascade impactor. Pulmonary absorptions of formulations were examined by the in situ pulmonary absorption described by Enna and Schanker method. The plasma concentration time profiles of rifampicin were constructed 8 hours following the intravenous and the intrapulmonary administrations. The pharmacokinetics parameters, Cmax, Tmax, t1/2, AUC, mean residence time (MRT, Ka and Ke were determined for each formulations. Results and major conclusions: The Tmax values for the samples decreased by increase in the amount of water in the initial feed. The Tmax values for the spray dried samples from the different mixtures of   dichloromethane and water were 60(min and 30(min respectively. The solvent mixture as the spray drying vehicle played an important role in the in vitro and in vivo lung deposition. The type of spray drying vehicle showed significant effect on the aerodynamic behavior and pharmacokinetic parameters of the particles. The pulmonary absorption of drug revealed the possibility of achieving the minimal inhibitory concentration (MIC of the antibiotics. The spray drying vehicle only affected absorption patterns of the formulations and it did not have any effect on the elimination rat of

  4. In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection

    Science.gov (United States)

    Colley, Thomas; Alanio, Alexandre; Kelly, Steven L.; Sehra, Gurpreet; Kizawa, Yasuo; Warrilow, Andrew G. S.; Parker, Josie E.; Kelly, Diane E.; Kimura, Genki; Anderson-Dring, Lauren; Nakaoki, Takahiro; Sunose, Mihiro; Onions, Stuart; Crepin, Damien; Lagasse, Franz; Crittall, Matthew; Shannon, Jonathan; Cooke, Michael; Bretagne, Stéphane; King-Underwood, John; Murray, John; Strong, Pete; Rapeport, Garth

    2017-01-01

    ABSTRACT The profile of PC945, a novel triazole antifungal designed for administration via inhalation, was assessed in a range of in vitro and in vivo studies. PC945 was characterized as a potent, tightly binding inhibitor of Aspergillus fumigatus sterol 14α-demethylase (CYP51A and CYP51B) activity (50% inhibitory concentrations [IC50s], 0.23 μM and 0.22 μM, respectively) with characteristic type II azole binding spectra. Against 96 clinically isolated A. fumigatus strains, the MIC values of PC945 ranged from 0.032 to >8 μg/ml, while those of voriconazole ranged from 0.064 to 4 μg/ml. Spectrophotometric analysis of the effects of PC945 against itraconazole-susceptible and -resistant A. fumigatus growth yielded IC50 (determined based on optical density [OD]) values of 0.0012 to 0.034 μg/ml, whereas voriconazole (0.019 to >1 μg/ml) was less effective than PC945. PC945 was effective against a broad spectrum of pathogenic fungi (with MICs ranging from 0.0078 to 2 μg/ml), including Aspergillus terreus, Trichophyton rubrum, Candida albicans, Candida glabrata, Candida krusei, Cryptococcus gattii, Cryptococcus neoformans, and Rhizopus oryzae (1 or 2 isolates each). In addition, when A. fumigatus hyphae or human bronchial cells were treated with PC945 and then washed, PC945 was found to be absorbed quickly into both target and nontarget cells and to produce persistent antifungal effects. Among temporarily neutropenic immunocompromised mice infected with A. fumigatus intranasally, 50% of the animals survived until day 7 when treated intranasally with PC945 at 0.56 μg/mouse, while posaconazole showed similar effects (44%) at 14 μg/mouse. This profile affirms that topical treatment with PC945 should provide potent antifungal activity in the lung. PMID:28223388

  5. Inhaler technique

    DEFF Research Database (Denmark)

    Levy, M L; Dekhuijzen, P R N; Barnes, P J

    2016-01-01

    Health professionals tasked with advising patients with asthma and chronic obstructive pulmonary disease (COPD) how to use inhaler devices properly and what to do about unwanted effects will be aware of a variety of commonly held precepts. The evidence for many of these is, however, lacking or old...... and therefore in need of re-examination. Few would disagree that facilitating and encouraging regular and proper use of inhaler devices for the treatment of asthma and COPD is critical for successful outcomes. It seems logical that the abandonment of unnecessary or ill-founded practices forms an integral part...... of this process: the use of inhalers is bewildering enough, particularly with regular introduction of new drugs, devices and ancillary equipment, without unnecessary and pointless adages. We review the evidence, or lack thereof, underlying ten items of inhaler 'lore' commonly passed on by health professionals...

  6. Determination of natural in vivo noble-gas concentrations in human blood.

    Directory of Open Access Journals (Sweden)

    Yama Tomonaga

    Full Text Available Although the naturally occurring atmospheric noble gases He, Ne, Ar, Kr, and Xe possess great potential as tracers for studying gas exchange in living beings, no direct analytical technique exists for simultaneously determining the absolute concentrations of these noble gases in body fluids in vivo. In this study, using human blood as an example, the absolute concentrations of all stable atmospheric noble gases were measured simultaneously by combining and adapting two analytical methods recently developed for geochemical research purposes. The partition coefficients determined between blood and air, and between blood plasma and red blood cells, agree with values from the literature. While the noble-gas concentrations in the plasma agree rather well with the expected solubility equilibrium concentrations for air-saturated water, the red blood cells are characterized by a distinct supersaturation pattern, in which the gas excess increases in proportion to the atomic mass of the noble-gas species, indicating adsorption on to the red blood cells. This study shows that the absolute concentrations of noble gases in body fluids can be easily measured using geochemical techniques that rely only on standard materials and equipment, and for which the underlying concepts are already well established in the field of noble-gas geochemistry.

  7. Ciclesonide Oral Inhalation

    Science.gov (United States)

    Ciclesonide oral inhalation is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma in adults ... Ciclesonide comes as an aerosol to inhale by mouth using an inhaler. Ciclesonide is usually inhaled twice ...

  8. Substance use - inhalants

    Science.gov (United States)

    Substance abuse - inhalants; Drug abuse - inhalants; Drug use - inhalants; Glue - inhalants ... Gases, such as butane (lighter fluid), computer cleaning spray, ... fast-drying glue, felt-tip marker, gasoline, nail polish remover, ...

  9. Tiotropium Oral Inhalation

    Science.gov (United States)

    ... a specially designed inhaler. You will use the inhaler to breathe in the dry powder contained in the capsules. Tiotropium is usually inhaled once a day in the morning or evening. To help you remember to inhale ... only work if you use the inhaler it comes with to inhale the powder in ...

  10. Property value estimation for inhaled therapeutic binary gas mixtures: He, Xe, N2O, and N2 with O2

    Directory of Open Access Journals (Sweden)

    Katz Ira

    2011-12-01

    Full Text Available Abstract Background The property values of therapeutic gas mixtures are important in designing devices, defining delivery parameters, and in understanding the therapeutic effects. In the medical related literature the vast majority of articles related to gas mixtures report property values only for the pure substances or estimates based on concentration weighted averages. However, if the molecular size or structures of the component gases are very different a more accurate estimate should be considered. Findings In this paper estimates based on kinetic theory are provided of density, viscosity, mean free path, thermal conductivity, specific heat at constant pressure, and diffusivity over a range of concentrations of He-O2, Xe-O2, N2O-O2 and N2-O2 mixtures at room (or normal and body temperature, 20 and 37°C, respectively and at atmospheric pressure. Conclusions Property value estimations have been provided for therapeutic gas mixtures and compared to experimental values obtained from the literature where possible.

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

    OpenAIRE

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

    2015-01-01

    Abstract Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA? dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung?) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo. Methods: Selected profiles, representative of the range of inhalation endpoints achieved...

  12. In vivo evaluation of the potential neurotoxicity of aerosols released from mechanical stress of nano-TiO2 additived paints in mice chronically exposed by inhalation

    Science.gov (United States)

    Manixay, S.; Delaby, S.; Gaie-Levrel, F.; Wiart, M.; Motzkus, C.; Bencsik, A.

    2017-06-01

    Engineered Nanomaterials (ENM) provide technical and specific benefits due to their physical-chemical properties at the nanometer scale. For instance, many ENM are used to improve products in the building industry. Nanoscaled titanium dioxide (TiO2) is one of the most used ENM in this industry. Incorporated in different matrix, cement, glass, paints… TiO2 nanoparticles (NPs) provide the final product with anti-UV, air purification and self-cleaning properties, thanks to their photocatalytic activity. However, ageing processes of such products, as photocatalytic paints, during a mechanical stress have been shown to release TiO2 NPs from this matrix associated with sanding dust. Thus, workers who sand painted walls could be exposed to TiO2 NPs through inhalation. As inhalation may lead to a translocation of particulate matter to the brain via olfactory or trigeminal nerves, there is an urgent need for evaluating a potential neurotoxicity. In order to provide new knowledge on this topic, we developed a dedicated experimental set-up using a rodent model exposed via inhalation. The aerosol released from a mechanical stress of photocatalytic paints containing TiO2 NPs was characterized and coupled to an exposition chamber containing group of mice free to move and chronically exposed (2 hours per day for 5 days a week during 8 weeks).

  13. Flunisolide Oral Inhalation

    Science.gov (United States)

    Flunisolide oral inhalation is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma in adults ... Flunisolide comes as an aerosol to inhale by mouth. It usually is inhaled twice daily. Try to ...

  14. Fluticasone Oral Inhalation

    Science.gov (United States)

    Fluticasone oral inhalation is used to prevent difficulty breathing, chest tightness, wheezing, and coughing caused by asthma in adults ... Fluticasone comes as an aerosol to inhale by mouth using an inhaler and as a powder to ...

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

    Science.gov (United States)

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

    2009-02-01

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

  16. Nickel subsulfide is genotoxic in vitro but shows no mutagenic potential in respiratory tract tissues of BigBlue rats and Muta Mouse mice in vivo after inhalation.

    Science.gov (United States)

    Mayer, C; Klein, R G; Wesch, H; Schmezer, P

    1998-12-03

    Carcinogenic nickel compounds are known to induce promutagenic DNA lesions such as DNA strand breaks and DNA adducts in cultured mammalian cells. In standard mutation assays, in contrast, they were found to be either inactive or weakly active. In our in vitro mutation studies in a lacI transgenic embryonic fibroblast cell line, nickel subsulfide (Ni3S2) increased mutation frequency up to 4. 5-fold. We subsequently applied the comet assay and transgenic rodent mutation assays to investigate the DNA damaging effect and mutagenic potential of nickel subsulfide in target cells of carcinogenesis. A 2-h in vitro treatment of freshly isolated mouse nasal mucosa and lung cells with nickel subsulfide clearly induced DNA fragmentation in a concentration dependent manner. The strong effect was not seen in the same cell types following inhalative treatment of mice and rats, leading only in the mouse nasal mucosa to high DNA damage. When the same inhalative treatment was applied to lacZ and lacI transgenic mice and rats, the spontaneous mutation frequency of these target genes in the respiratory tissues was not increased. These results support a recently proposed non-genotoxic model of nickel carcinogenesis, which acts through gene silencing via DNA methylation and chromatin condensation. This model may also explain our in vitro mutation data in the lacI transgenic cell line, in which nickel subsulfide increased mutation frequency, but in about one-third of the mutants, molecular analysis did not reveal any DNA sequence change in the coding region of the lacI gene despite of the phenotypic loss of its function. Copyright 1998 Elsevier Science B.V.

  17. In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe.

    Directory of Open Access Journals (Sweden)

    Zackary I Cleveland

    Full Text Available BACKGROUND: Hyperpolarized (HP (129Xe magnetic resonance imaging (MRI permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10% and large chemical shift range (>200 ppm in tissues allow HP (129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP (129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP (129Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP (129Xe signal. METHODS AND PRINCIPAL FINDINGS: Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse (129Xe into the arterial blood of live rats with an extracorporeal (EC circuit. The resulting gas-phase (129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm(3. We also show that the (129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. CONCLUSIONS: Extracorporeal infusion of HP (129Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow (129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP (129Xe.

  18. In vitro and in vivo preclinical profile of abediterol (LAS100977), an inhaled long-acting β2-adrenoceptor agonist, compared with indacaterol, olodaterol and vilanterol.

    Science.gov (United States)

    Aparici, Mònica; Gavaldà, Amadeu; Ramos, Israel; Carcasona, Carla; Otal, Raquel; Fernández-Blanco, Joan Antoni; Montero, Jose Luís; García, Vicente Marco; López, Rosa; De Alba, Jorge; Doe, Christopher; Puig, Carlos; Vilella, Dolors; Miralpeix, Montserrat

    2016-01-05

    Abediterol is a novel long-acting β2-adrenoceptor agonist (LABA) currently in development for once-daily combination maintenance therapy of asthma and COPD. This study investigated the preclinical profile of abediterol in terms of affinity, potency, selectivity, duration of action and cardiac effects in comparison to the marketed once-daily LABAs indacaterol, olodaterol and vilanterol. Abediterol was the compound with the highest in vitro potency for dog, guinea pig and human β2-adrenoceptors. In electrical field stimulated guinea pig trachea, abediterol demonstrated 5-, 44- and 77-fold greater potency than olodaterol, indacaterol and vilanterol, respectively. In anaesthetised guinea pigs, inhaled abediterol was also the most potent compound, with 5-20 times higher bronchoprotective potency than other once-daily LABAs against acetylcholine. The bronchoprotective half-life of abediterol in guinea pigs was 36h compared with 51h for indacaterol, 47h for olodaterol, and 18h for vilanterol. In anaesthetised dogs, abediterol also inhibited acetylcholine-induced bronchoconstriction, with higher potency than olodaterol and vilanterol [ID40 (dose inhibiting bronchoconstriction by 40%) of 0.059µg/kg, 0.180µg/kg and 2.870µg/kg, respectively]. In parallel, effects on heart rate in dogs were also measured. Abediterol showed greater safety index (defined as the ratio of the maximal dose without effect on heart rate and the ID40) than olodaterol and vilanterol (10.5 versus 4.9 and 2.4, respectively). Taken together, these data suggest that abediterol offers potent bronchodilation and a sustained duration of action suited to once-daily dosing, plus a reduced potential for class-related cardiac side effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Ipratropium Oral Inhalation

    Science.gov (United States)

    Ipratropium oral inhalation is used to prevent wheezing, shortness of breath, coughing, and chest tightness in people with chronic ... comes as a solution (liquid) to inhale by mouth using a nebulizer (machine that turns medication into ...

  20. Asthma Inhalers: Which One's Right for You?

    Science.gov (United States)

    ... dose inhaler Metered dose inhaler with a spacer Dry powder inhaler Small and convenient to carry. Less convenient to ... t use a standard metered dose inhaler or dry powder inhaler. Other types include: Metered dose inhaler with a ...

  1. Evaluation of a gas in vitro system for predicting methane production in vivo

    DEFF Research Database (Denmark)

    Danielsson, Rebecca; Ramin, Mohammad; Bertilsson, Jan

    2017-01-01

    Methane production from ruminant livestock varies with the diet as a result of factors such as dry matter intake, diet composition, and digestibility. To estimate the effect of dietary composition and feed additives, CH4 production can be measured in vitro as a first step because large numbers...... of samples can be incubated and analyzed at the same time. This study evaluated a recently developed in vitro method for prediction of in vivo CH4 production by examining the relationship between predicted and observed CH4 production values. A total of 49 different diets (observations), used in previous 13...... in vivo studies, were selected to include diets varying in nutrient composition. Methane production was measured in all in vivo studies by respiration chambers or the GreenFeed system (C-Lock Inc., Rapid City, SD). Overall, the in vitro system predicted CH4 production well (R2 = 0.96), but the values...

  2. A method for determining an indicator of effective dose calculation due to inhalation of Radon and its progeny from in vivo measurements; Um metodo para determinar um indicador para calcular dose efetiva devida a inalacao de Radonio e seus descendentes utilizando medicoes in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Estrada, Julio Jose da Silva

    1994-07-01

    Direct measurement of the absolved dose to lung tissue from inhalation of radon and its progeny is not possible and must be calculated using dosimetric models, taking into consideration the several parameters upon which the dose calculation depends. To asses the dose due to inhalation of radon and its progeny, it is necessary to estimate the cumulative exposure. Historically, this has been done using WLM values estimated with measurements of radon concentration in air. The radon concentration in air varies significantly, however, in space with time, and the exposed individual is also constantly moving around. This makes it almost impossible to obtain a precise estimate of an individual's inhalation exposure. This work describes a pilot study to calculate lung dose from the deposition of radon progeny, via estimates of cumulative exposure derived from in vivo measurements of {sup 210} Pb, in subjects exposed to above-average radon and its progeny concentrations in their home environments. The measurements were performed in a whole body counter. With this technique, the exposed individuals become, in affect, their own samplers and dosimeters and the estimate of cumulative exposure is not affected by the variation of the atmospheric concentration of radon and its progeny in time and space. Forty individuals identified as living in homes with radon levels ranging from about 740 Bq/m{sup 3} to 150.000 Bq/m{sup 3} were measured. Also, additional 34 measurements were made on personnel from NYUMC/NIEM who live in a residential area surrounding the laboratory in which the levels of radon have been shown to be at below average values. To realize these measurements a methodology was developed to determine the subject's background, using a head phantom made with a cubic plastic container containing known amounts of potassium and calcium dissolved in four liters of water. The effective doses calculated from the in vivo measurements are compared to effective doses

  3. Review of the TAIFUN multidose dry powder inhaler technology.

    Science.gov (United States)

    Overhoff, Kirk A; Clayborough, Robert; Crowley, Michael

    2008-09-01

    Although pressurized metered dose inhalers (pMDIs) currently constitute a majority of the market share in the inhalation market, dry powder inhaler (DPI) products have become increasingly popular due to their reliability and product performance. One such DPI is the TAIFUN inhaler that is a reservoir-based DPI system with the ability to produce consistent and uniform doses in vitro. Originally developed for the pulmonary delivery of salbutamol, the TAIFUN inhaler platform has since been used to develop a product for breakthrough cancer pain management using fentanyl citrate as the active drug. In vivo results show the TAIFUN inhaler is able to deliver a rapid onset of action and increased relative bioavailability compared with other fentanyl products currently on the market.

  4. [Acute rhabdomyolysis due to butane inhalation. Report of two cases].

    Science.gov (United States)

    Khatouf, M; Ifkharen, B; Drissi, M; Housni, B; Harandou, M; Kanjaa, N

    2004-11-01

    Prolonged inhalation of gas butane induced mostly neurological and cardiovascular symptoms. We reported two very rare cases of acute rhabdomyolysis caused by accidental prolonged inhalation of butane. The early diagnosis and the symptomatic treatment were associated with favourable evolution in the two cases. The mechanism of this complication is discussed and compared with the literature.

  5. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    Science.gov (United States)

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  6. Gas chromatographic-mass spectrometric analysis of sulfur mustard-plasma protein adducts: validation and use in a rat inhalation model.

    Science.gov (United States)

    Capacio, Benedict R; Smith, J Richard; Lawrence, Richard J; Boyd, Brian L; Witriol, Alicia M; Conti, Michele L; Collins, Jennifer L; Sciuto, Alfred M

    2008-01-01

    Sulfur mustard (HD) is an alkylating agent that reacts rapidly with macromolecular targets resulting in the formation of stable adducts providing depots for markers of exposure. The purpose of this study was to validate an analytical procedure for detection of HD-plasma protein adducts and to establish the utility of the method in an HD rat inhalation study. Calibration curves were prepared in human and rat plasma at six levels of HD (12.5 to 400 nM). Correlation coefficients for the mean data were 0.9987 for human and 0.9992 for rat plasma. The percent coefficient of variation (%CV) derived from the mean concentration data ranged from 0.53 to 14.1% in human (n = 5) and 0.57 to 10.63% in rat (n = 6) plasma. Intraday and interday precision and accuracy studies were conducted at three concentration levels (25, 150, 300 nM) to represent low, medium, and high concentrations of HD relative to those employed in the calibration curve. Precision and accuracy were assessed by determining %CV and % error, respectively. For intra- and interday studies, the %CVs and absolute % errors were less than 15%. The limits of quantitation were 20.88 nM for human and 16.73 nM for rat plasma. In animal studies, rats received nebulized HD at six doses. The data indicate a dose-dependent relationship between maximal plasma concentrations and dose administered (R(2) = 0.9728). Results from this study indicate an accurate, precise, and sensitive method. The method was useful in determining plasma protein adduct formation in a rat inhalation model.

  7. Objective measurement of inhaler inhalation flow profile using acoustic methods

    Energy Technology Data Exchange (ETDEWEB)

    Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

    2016-07-01

    Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

  8. Scatter Correction with Combined Single-Scatter Simulation and Monte Carlo Simulation Scaling Improved the Visual Artifacts and Quantification in 3-Dimensional Brain PET/CT Imaging with 15O-Gas Inhalation.

    Science.gov (United States)

    Magota, Keiichi; Shiga, Tohru; Asano, Yukari; Shinyama, Daiki; Ye, Jinghan; Perkins, Amy E; Maniawski, Piotr J; Toyonaga, Takuya; Kobayashi, Kentaro; Hirata, Kenji; Katoh, Chietsugu; Hattori, Naoya; Tamaki, Nagara

    2017-12-01

    In 3-dimensional PET/CT imaging of the brain with 15O-gas inhalation, high radioactivity in the face mask creates cold artifacts and affects the quantitative accuracy when scatter is corrected by conventional methods (e.g., single-scatter simulation [SSS] with tail-fitting scaling [TFS-SSS]). Here we examined the validity of a newly developed scatter-correction method that combines SSS with a scaling factor calculated by Monte Carlo simulation (MCS-SSS). Methods: We performed phantom experiments and patient studies. In the phantom experiments, a plastic bottle simulating a face mask was attached to a cylindric phantom simulating the brain. The cylindric phantom was filled with 18F-FDG solution (3.8-7.0 kBq/mL). The bottle was filled with nonradioactive air or various levels of 18F-FDG (0-170 kBq/mL). Images were corrected either by TFS-SSS or MCS-SSS using the CT data of the bottle filled with nonradioactive air. We compared the image activity concentration in the cylindric phantom with the true activity concentration. We also performed 15O-gas brain PET based on the steady-state method on patients with cerebrovascular disease to obtain quantitative images of cerebral blood flow and oxygen metabolism. Results: In the phantom experiments, a cold artifact was observed immediately next to the bottle on TFS-SSS images, where the image activity concentrations in the cylindric phantom were underestimated by 18%, 36%, and 70% at the bottle radioactivity levels of 2.4, 5.1, and 9.7 kBq/mL, respectively. At higher bottle radioactivity, the image activity concentrations in the cylindric phantom were greater than 98% underestimated. For the MCS-SSS, in contrast, the error was within 5% at each bottle radioactivity level, although the image generated slight high-activity artifacts around the bottle when the bottle contained significantly high radioactivity. In the patient imaging with 15O2 and C15O2 inhalation, cold artifacts were observed on TFS-SSS images, whereas no

  9. Pediatric inhalation injury

    OpenAIRE

    Sen, Soman

    2017-01-01

    Smoke inhalation injury can cause severe physiologic perturbations. In pediatric patients, these perturbations cause profound changes in cardiac and pulmonary physiology. In this review, we examine the pathology, early management options, ventilator strategy, and long-term outcomes in pediatric patients who have suffered a smoke inhalation injury.

  10. Reasons for Inhalant Use.

    Science.gov (United States)

    Joe, George W.; Simpson, D. Dwayne

    1991-01-01

    Among 110 Mexican-American adolescents in a Texas drug abuse program, initial use of toxicant inhalants was related to availability and sensation-seeking, followed by psychological problems, parental and home problems, and peer influence. Quitting inhalant use was related to social pressures, attitude change, and perceived health risks. (Author/SV)

  11. Evaluation of a gas in vitro system for predicting methane production in vivo

    DEFF Research Database (Denmark)

    Danielsson, Rebecca; Ramin, Mohammad; Bertilsson, Jan

    2017-01-01

    Methane production from ruminant livestock varies with the diet as a result of factors such as dry matter intake, diet composition, and digestibility. To estimate the effect of dietary composition and feed additives, CH4 production can be measured in vitro as a first step because large numbers...... known to affect CH4 production such as dry matter intake, digestibility, and dietary concentrations of fat and starch. However, some factors included in the model were not well predicted by the system, with residuals negatively related to neutral detergent fiber concentration and positively related...... obtained were slightly underestimated compared with observed in vivo values (mean 399 L/d compared with 418 L/d: root mean square prediction error = 51.6 L/d or 12.3% of observed mean). Further analysis of the effect on residuals showed no significant relationship between CH4 production and most factors...

  12. Inhalants in Peru.

    Science.gov (United States)

    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

  13. Inhalation therapy in children

    Directory of Open Access Journals (Sweden)

    Jolanta Pietrzak

    2014-12-01

    Full Text Available Inhalation is a form of treatment used in respiratory diseases that allows medications to be administered directly to the affected site. Thanks to this, the administration of lower doses helps obtain a higher concentration in the target organ and eliminate or effectively reduce systemic adverse effects. For drug deposition in the respiratory system, we use inhalers (pressurised, dry powder, soft mist or nebulisers (jet, ultrasonic, vibrating mesh. In pressurised inhalers, spacers or holding chambers can be used to effectively synchronise inspiration with dose release. Inhalers are indicated in lower respiratory tract diseases, and the only contraindication is the inability to use the device. Nebulisers can be used in upper and lower respiratory tract diseases, but there are certain contraindications (among others: acute inflammation, flares of chronic diseases, circulatory insufficiency. The selection of an inhaler (or a shift to another device must be justified. It should be based on the knowledge of the properties and principles of individual inhalers, assessment of the child’s ability to use the device properly (including obtaining optimal inspiratory flows as well as on the preferences of patients and their guardians. It is significant to individually instruct the patient how to use an inhaler when this treatment is being implemented and to review the inhalation technique during each follow-up visit. Treatment benefits can be achieved when age, clinical condition, proper inhalation technique correlated with the abilities of patients are considered.

  14. Two /sup 238/Pu inhalation incidents

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, R.R.; Hall, R.M.

    1978-06-01

    Two employees inhaled significant amounts of /sup 238/Pu in separate unrelated contamination incidents in 1977. Both acute exposure incidents are described and the urine, feces, and in-vivo chest count data for each employee. Case B (/sup 238/PuNO/sub 3/) received 24 DTPA treatments beginning the day of the incident while, for medical reasons, Case A (/sup 238/PuO/sub 2/) received no therapy.

  15. Albuterol Oral Inhalation

    Science.gov (United States)

    ... Corgard), and propranolol (Inderal); digoxin (Lanoxin); diuretics ('water pills'); epinephrine (Epipen, Primatene Mist); other inhaled medications used to relax the air passages such as metaproterenol and levalbuterol (Xopenex); and ...

  16. Levalbuterol Oral Inhalation

    Science.gov (United States)

    ... and propranolol (Inderal); digoxin (Digitek, Lanoxin); diuretics ('water pills'); epinephrine (Epipen, Primatene Mist); medications for colds; and other inhaled medications to relax the air passages such as metaproterenol (Alupent) and pirbuterol (Maxair). ...

  17. Umeclidinium Oral Inhalation

    Science.gov (United States)

    ... breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, that includes chronic bronchitis and emphysema). Umeclidinium inhalation is in a class of medications ...

  18. Olodaterol Oral Inhalation

    Science.gov (United States)

    ... breath, coughing, and chest tightness caused by chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways, which includes chronic bronchitis and emphysema). Olodaterol oral inhalation is in a class of ...

  19. Improvement of Brain Tissue Oxygenation by Inhalation of Carbogen

    DEFF Research Database (Denmark)

    Ashkanian, M.; Borghammer, P.; Gjedde, A.

    2008-01-01

    Hyperoxic therapy for cerebral ischemia is suspected to reduce cerebral blood flow (CBF), due to the vasoconstrictive effect of oxygen on cerebral arterioles. We hypothesized that vasodilation predominates when 5% CO(2) is added to the inhaled oxygen (carbogen). Therefore, we used positron emission...... tomography (PET) to measure CBF and cerebral metabolic rate of oxygen (CMRO(2)) during inhalation of test gases (O(2), CO(2), carbogen and atmospheric air) in 10 healthy volunteers. Arterial blood gases were recorded during administration of each gas. The data were analyzed with volume-of-interest and voxel......-based statistical methods. Inhalation of CO(2) or carbogen significantly increased global CBF, whereas pure oxygen decreased global CBF. The CMRO(2) generally remained unchanged, except in white matter during oxygen inhalation relative to condition of atmospheric air inhalation. The volume-of-interest results were...

  20. Comparison of the cohesion-adhesion balance approach to colloidal probe atomic force microscopy and the measurement of Hansen partial solubility parameters by inverse gas chromatography for the prediction of dry powder inhalation performance.

    Science.gov (United States)

    Jones, Matthew D; Buckton, Graham

    2016-07-25

    The abilities of the cohesive-adhesive balance approach to atomic force microscopy (AFM) and the measurement of Hansen partial solubility parameters by inverse gas chromatography (IGC) to predict the performance of carrier-based dry powder inhaler (DPI) formulations were compared. Five model drugs (beclometasone dipropionate, budesonide, salbutamol sulphate, terbutaline sulphate and triamcinolone acetonide) and three model carriers (erythritol, α-lactose monohydrate and d-mannitol) were chosen, giving fifteen drug-carrier combinations. Comparison of the AFM and IGC interparticulate adhesion data suggested that they did not produce equivalent results. Comparison of the AFM data with the in vitro fine particle delivery of appropriate DPI formulations normalised to account for particle size differences revealed a previously observed pattern for the AFM measurements, with a slightly cohesive AFM CAB ratio being associated with the highest fine particle fraction. However, no consistent relationship between formulation performance and the IGC data was observed. The results as a whole highlight the complexity of the many interacting variables that can affect the behaviour of DPIs and suggest that the prediction of their performance from a single measurement is unlikely to be successful in every case. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Thoracic fraction of inhaled fiber aerosol.

    Science.gov (United States)

    Cheng, Yung Sung; Su, Wei-Chung

    2013-01-01

    Size-selective sampling is a health-related method to collect airborne particles based on penetration of inhaled particles into different regions of the human respiratory tract; thus, it is the most relevant sampling method to correlate health risks with occupational exposure. The current practice of sampling asbestos and other fibers is not a size-selective method. The thoracic size fraction, defined as the portion of inhaled particles that can penetrate through the larynx, has been suggested as the most relevant size-selective sampling method for fiber aerosol. The thoracic fraction is based on 1-deposition of inhaled spherical particles in the human extrathoracic airways for mouth breathing and corrected for the particle inhalability. There is no comparable information for fiber aerosols; therefore, there is no technical basis to ascertain whether the current thoracic fraction definition is suitable for fiber aerosols. No human data are available from controlled experiments of inhaled fiber aerosols for the obvious reason that most fiber materials are potentially hazardous when inhaled. Our approach was to measure penetration of fiber aerosol in realistic human oropharyngeal airway replicas and to compare that with data from spherical particles. We showed that realistic human oral airway replicas (including the oral cavity, pharynx, and larynx regions) provided useful spherical and fiber particle deposition in the human head airway. These data could be used to test the thoracic fraction curves. The spherical penetration is in agreement with human in vivo data used to establish the thoracic fraction curve. Fiber penetrations through the larynx of two human oral airway replicas were higher than those for spherical particles for the same aerodynamic diameter using the same replicas. The thoracic curve as defined for spherical particles, therefore, may not include some fibers that could penetrate to the thoracic region.

  2. Effectiveness of Inhalant Abuse Legislation.

    Science.gov (United States)

    Batis, Jeffery C

    2017-01-28

    Since peaking in the 1990s, inhalant abuse has steadily decreased over the past two decades. Concurrently, nearly every state has passed legislation aimed at minimizing inhalant abuse. While males have historically been more likely to abuse inhalants than females, there is no longer a sex effect in self-reported rates of inhalant abuse. The objective of the present study is to evaluate the effect of anti-inhalant abuse legislation on self-reported rates of inhalant abuse, in high school age males and females. Beginning in 1993, the CDC's biannual Youth Risk Behavior Surveillance Survey asked respondents if they have ever used inhalants to get high. Data from these surveys were collected, along with the date of passage of anti-inhalant abuse legislation in 46 of 50 states. ANOVAs were conducted to assess the effect of legislation on self-reported inhalant abuse rates. There were no significant main effects or interactions that demonstrated that inhalant abuse rates decreased in males or females following passage of legislation aimed at decreasing inhalant abuse. Conclusion/Importance: To date, 46 of 50 states have passed laws aimed at minimizing inhalant abuse, and while inhalant abuse rates have been decreasing for the past two decades, there is no evidence that this decline is related to enactment of these laws. Further research is needed to determine the cause of the decrease in inhalant abuse. The laws may benefit from amendments to include options for treatment.

  3. Inhalation delivery of proteins from ethanol suspensions.

    Science.gov (United States)

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

    2001-09-25

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

  4. [Inhaled medication in pediatrics].

    Science.gov (United States)

    Sapet, A; Oudyi, M; Dubus, J-C

    2013-08-01

    Three different devices are available for inhaled medications in children: the pressurized metered dose inhalers (pMDIs, breath-actuator synchronized pMDI, and valved holding spacers), the dry powder inhalers, and the nebulizers. To choose the better device for a particular patient, a perfect knowledge of the available devices, of their mode of use, of their advantages and inconvenient is required. The use of a pMDI coupled to a valved holding spacer is the first mode of delivery to propose in children aged less than 6 years. After 6 years old, the DPIs may be proposed depending on the child's competences. At last, the nebulizations are indicated in some particular and severe indications, but new indications are appearing because of recent progresses. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Nicotine microaerosol inhaler.

    Science.gov (United States)

    Andrus, P G; Rhem, R; Rosenfeld, J; Dolovich, M B

    1999-01-01

    To measure the droplet size distribution of a nicotine pressurized metered-dose inhaler using a nicotine in ethanol solution formulation with hydrofluoroalkane as propellant. Sizing was performed at room temperature by multistage liquid impinger and quartz crystal impactor. The mass median aerodynamic diameter of the nicotine aerosol produced was measured at 1.6 mm by multistage liquid impinger and 1.5 mm by quartz crystal impactor. The inhaler formulation used produces a microaerosol of sufficiently fine droplet size that mimics the puff-by-puff pulmonary arterial bolus nicotine delivery of tobacco smoke. The absence of combustion products such as heat, carcinogens and carbon monoxide permits safer nicotine delivery via the inhaler than is possible via smoked tobacco.

  6. Inhaled Corticosteroids (ICSs) and Pregnancy

    Science.gov (United States)

    Inhaled Corticosteroids (ICSs) In every pregnancy, a woman starts out with a 3-5% chance of having a baby ... This sheet talks about whether exposure to inhaled corticosteroids may increase the risk for birth defects over ...

  7. Who Can Use an Inhaler?

    Science.gov (United States)

    ... Should You Go to School? Breast Cancer Who Can Use an Inhaler? KidsHealth > For Kids > Who Can Use an Inhaler? Print A A A en ... get medicine right into your lungs , where it can help stop breathing problems related to asthma. Inhalers ...

  8. Budesonide Oral Inhalation

    Science.gov (United States)

    ... hands, feet, ankles, or lower legs hoarseness difficulty breathing or swallowing wheezing cough chest pain anxiety fever, chills, or other signs of infection tiredness nausea vomiting weakness changes in vision Budesonide inhalation may cause children to grow more slowly. There is not enough ...

  9. Inhalational Lung Disease

    Directory of Open Access Journals (Sweden)

    MR Farzaneh

    2010-01-01

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

  10. Practical Perspectives On The In-Vitro And In-Vivo Evaluation Of A Fiber Optic Blood Gas Sensor

    Science.gov (United States)

    Hansmann, Douglas R.; Gehrich, John L.

    1988-06-01

    A new optical fluorescence-based microsensor has been developed to continuously monitor intra-arterial blood gases (pH, pCO2, p02) with a probe sufficiently small to share the lumen of a 20 gauge arterial catheter without compromising pressure fidelity or ease of blood withdrawal. The evaluation of performance has proceeded through a combination of in-vitro, animal and clinical studies. Each has had its own unique problems. This series of studies has re-emphasized the fact that acceptable clinical performance of even the best designed systems is not assured by success in in-vitro or even animal studies. In-vitro studies were conducted to quantify the precision and time response of the sensors and to obtain an assessment of performance characteristics in the in-vitro environment. System precision (1 S.D.) in tonometered bovine blood was 0.03 (pH units), 2 mm Hg (pCO2), and 4 mm Hg (p02). These results were collected over 40 points at two different temperatures (28 and 37 F). Average drift measured over a 200 hour continuous study period showed 0.005 pH units, 0.9 mm Hg pCO2, and 2.1 mm Hg p02 per 24 hour period. In-vivo animal studies (dog, pig, sheep, and rabbit) demonstrated the need for antithrombogenic materials. The probe system employs a covalently bound Heparin coating. However, maintenance of a patent IV drip line and adequate arterial flow was found to be critical. With proper attention to these factors, overall probe performance was found to be equivalent to that predicted by the in-vitro studies. Clinical trials in volunteers, and in critical care and surgical patients, have re-affirmed the need for antithrombogenic probe materials and adequate arterial blood flow. In addition, human studies revealed factors which can lead to sensor offsets, unless properly compensated by probe design. Subsequent clinical trials in volunteers and clinical subjects have verified that continuous monitoring of blood gases is feasible with accuracies approaching that of the

  11. Inhaler treatment options in COPD

    Directory of Open Access Journals (Sweden)

    S. P. Newman

    2005-12-01

    Full Text Available A variety of inhaler devices are available for delivering treatments to patients with chronic obstructive pulmonary disease, and new inhalers are currently being developed. Each type of device has advantages and disadvantages, and the methods of preparation and use vary between them. The differences in instructions for use can easily confuse patients and health providers alike, resulting in incorrect use of many inhalers. "Crucial" errors in inhaler technique, whereby no drug is deposited in the lungs, must be avoided. Any type of inhaler can be misused so that little or no drug is deposited in the lungs. It is now increasingly widely recognised that a successful treatment outcome in chronic obstructive pulmonary disease depends as much on the inhaler device as it does on the drug. Inhaler choice in chronic obstructive pulmonary disease should take into account whether the patient is likely to use it correctly, as well as patient preference and the likelihood of adherence to treatment.

  12. Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO) : a randomised controlled trial

    NARCIS (Netherlands)

    Mercier, Jean-Christophe; Hummler, Helmut; Durrmeyer, Xavier; Sanchez-Luna, Manuel; Carnielli, Virgilio; Field, David; Greenough, Anne; Van Overmeire, Bart; Jonsson, Baldvin; Hallman, Mikko; Baldassarre, James

    2010-01-01

    Background In animal models, inhaled nitric oxide improved gas exchange and lung structural development, but its use in premature infants at risk of developing bronchopulmonary dysplasia remains controversial. We therefore tested the hypothesis that inhaled nitric oxide at a low concentration,

  13. Digestion of wood-based hemicellulose extracts as screened by in vitro gas production method and verified in vivo using sheep

    Directory of Open Access Journals (Sweden)

    Marketta Rinne

    2016-03-01

    Full Text Available The objective of the present study was to evaluate the potential of pressurized hot water extracted hemicellulose fractions from various wood species as feeds for ruminants. In Experiment 1, the fermentability of several hemicellulose extracts was screened using an in vitro gas production method. The samples were extracted from spruce (Picea abies including mainly galactoglucomannan (GGM, from birch (Betula pendula consisting mainly of xylan and from larch (Larix sibirica consisting mainly of arabinogalactan. The GGM and xylan samples were readily fermented by rumen microbes while arabinogalactan was not. Based on the in vitro study, GGM was chosen for an in vivo digestibility trial using sheep, where it was fed at increasing proportions of diet dry matter (0, 47, 94 and 141 g kg-1 in a Latin Square design. The in vivo organic matter digestibility of GGM was relatively low, 0.58, but PHWE extracted hemicellulose has some potential as a feed for ruminants.

  14. Inhalation exposure methodology.

    OpenAIRE

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and ga...

  15. [A basic study for estimating the level of exposure to a nasal inhalant containing a stimulant].

    Science.gov (United States)

    Ando, H; Shimizu, H; Takahashi, Y; Fukumoto, M; Okonogi, H; Kadokura, M

    1993-08-01

    Criminal cases involving stimulant abuse have increased since 1970 but have now leveled off. Some of the offenders claimed to have used the Vicks Inhaler containing a stimulant (1-methamphetamine) which is used for the treatment of nasal obstruction. The aim of this experiment was to measure the amount of 1-methamphetamine contained in the Vicks Inhaler by stimulating the human respiratory system. The results are as follows: 1) The data from the stimulation experiment showed that the inhalation level of 1-methamphetamine was estimated to be 320.4ng. From this value, the level of 1-methamphetamine absorbed per one respiration was calculated to be 21ng. 2) The data from quantitative and qualitative analysis by gas-chromatography showed that menthol interfered with the methamphetamine. 3) A qualitative test for the stimulant in urine was negative when the subject inhaled the Vicks Inhaler only once. However, this test turned positive when the subject inhaled it more than 17 times.

  16. American Indian adolescent inhalant use.

    Science.gov (United States)

    Thurman, P J; Green, V A

    1997-01-01

    Inhalant use and use patterns, decision-making pertaining to inhalant use, cognitive capacity, cognitive egocentrism, and adherence to traditional ways were studied in a sample of male and female American Indian adolescents residing in a boarding home. Significant differences were not found for gender. Inhalant use group differences were found for only one variable, participation in tribal activities. For males, cognitive ability, cognitive egocentrism and participation in tribal activities were significant predictors of inhalant use/non-use. For females, tribal activities was the only significant predictor.

  17. Predicting Ventilation Failure in Children with Inhalation Injury.

    Science.gov (United States)

    1994-08-01

    tracheobron- supported adequately by mechanical ventilation would chitis and oxygenation abnormalities after 2 to 4 weeks of allow rapid enrollment of...these patients in trials of mechanical ventilation . Ventilatory indexes obtained early in new support techniques such as extracorporeal CO2 the...not be adequately supported by mechanical ventilation after smoke monary ventilation , combined liquid-gas ventilation , inhalation injury. Early

  18. In vitro gas and methane production of silages from whole-plant corn harvested at 4 different stages of maturity and a comparison with in vivo methane production.

    Science.gov (United States)

    Macome, F M; Pellikaan, W F; Hendriks, W H; Dijkstra, J; Hatew, B; Schonewille, J T; Cone, J W

    2017-11-01

    The current study investigated the relationship between in vitro and in vivo CH4 production by cows fed corn silage (CS)-based rations. In vivo CH4 production was measured in climate respiration chambers using 8 rumen-cannulated Holstein-Friesian cows. In vitro CH4 production was measured using rumen fluid from the 8 cows that were fully adapted to their respective experimental rations. The animals were grouped in 2 blocks, and randomly assigned to 1 of the 4 total mixed rations (TMR) that consisted of 75% experimental CS, 20% concentrate, and 5% wheat straw [dry matter (DM) basis]. The experimental CS were prepared from whole-plant corn that was harvested at either a very early (25% DM), early (28% DM), medium (32% DM), or late (40% DM) stage of maturity. The 4 experimental TMR and the corresponding CS served as substrate in 2 separate in vitro runs (each run representing 1 block of 4 animals) using rumen fluid from cows fed the TMR in question. No relationship was found between in vivo CH4 production and in vitro CH4 production measured at various time points between 2 and 48 h. None of the in vitro gas production (GP) and CH4 production parameters was influenced by an interaction between substrate and origin of rumen fluid. In vitro measured 48-h GP was not affected by the maturity of whole-plant corn, irrespective whether CS alone or as part of TMR was incubated in adapted rumen inoculum. Incubation of the experimental TMR did not affect the kinetics parameters associated with gas or CH4 production, but when CS alone was incubated the asymptote of GP of the soluble fraction was slightly decreased with increasing maturity of CS at harvest. In vitro CH4 production expressed as a percent of total gas was not affected by the maturity of whole-plant corn at harvest. Several in vitro parameters were significantly affected (GP) or tended to be affected (CH4) by diet fed to donor cows. It was concluded that the current in vitro technique is not suitable to predict in

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

    Science.gov (United States)

    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.

  20. Pulmonary and heart diseases with inhalation of atmospheric pressure plasma flow

    Science.gov (United States)

    Hirata, Takamichi; Murata, Shigeru; Kishimoto, Takumi; Tsutsui, Chihiro; Kondo, Akane; Mori, Akira

    2012-10-01

    We examined blood pressure in the abdominal aorta of mini pig under plasma inhalation of atmospheric pressure plasma flow. The coaxial atmospheric pressure plasma source has a tungsten wire inside a glass capillary, that is surrounded by a grounded tubular electrode. Plasma was generated under the following conditions; applied voltage: 8 kVpp, frequency: 3 kHz, and helium (He) gas flow rate: 1 L/min. On the other hand, sphygmomanometry of a blood vessel proceeded using a device comprising a disposable force transducer, and a bedside monitor for simultaneous electrocardiography and signal pressure measurements. We directly measured Nitric oxide (NO) using a catheter-type NO sensor placed in the coronary sinus through an angiography catheter from the abdomen. Blood pressure decreased from 110/65 to 90/40 mm Hg in the animals in vivo under plasma inhalation. The NO concentration in the abdominal aorta like the blood pressure, reached a maximum value at about 40 s and then gradually decreased.

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... metered dose inhaler one to two inches from mouth Your browser does not support iframes Using a ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a ...

  2. Asymptomatic inhaled foreign body

    Science.gov (United States)

    Salim, Muhammad U.; Asghar, Asif; Tareen, Irum; Azhar, Muhammad

    2016-01-01

    It is very rare to have a big foreign body in the lungs without any complications or symptoms for 2 years. A 14-year-old male with episodes of minor hemoptysis for 4 weeks had a history of inhalation of a bullet 2 years earlier. He had asymptomatic for lung complications for 2 years. The bullet was removed by right thoracotomy and non-anatomical wedge stapled resection, and he followed an uneventful recovery. An aspirated foreign body although big can remain asymptomatic for a long time, especially if it has migrated to the periphery. PMID:27652366

  3. Accidental condom inhalation.

    Science.gov (United States)

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

    2004-01-01

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

  4. Type I interferon and pattern recognition receptor signaling following particulate matter inhalation

    Directory of Open Access Journals (Sweden)

    Erdely Aaron

    2012-07-01

    Full Text Available Abstract Background Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc – stainless steel (GMA-SS welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. Results The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10. In addition, pulmonary expression of interferon α and β and Irf7 specific pattern recognition receptors (PRR and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3 were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88 to inhalation of GMA-SS. Conclusion This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure.

  5. In vivo Mapping of Local Cerebral Blood Flow by Xenon-Enhanced Computed Tomography

    Science.gov (United States)

    Gur, David; Good, Walter F.; Wolfson, Sidney K.; Yonas, Howard; Shabason, Leonard

    1982-03-01

    A noninvasive technique has been developed to measure and display local cerebral blood flow (LCBF) in vivo. In this procedure, nonradioactive xenon gas is inhaled and the temporal changes in radiographic enhancement produced by the inhalation are measured by sequential computerized tomography. The time-dependent xenon concentrations in various anatomical units in the brain are used to derive both the local partition coefficient and the LCBF. Functional mapping of blood flow with excellent anatomical specificity has been obtained in the baboon brain. The response of LCBF to stimuli such as changes in carbon dioxide concentrations as well as the variability in LCBF in normal and diseased tissue can be easily demonstrated. This method is applicable to the study of human physiology and pathologic blood flow alterations.

  6. Intrahepatic gas at postmortem computed tomography: forensic experience as a potential guide for in vivo trauma imaging.

    Science.gov (United States)

    Jackowski, Christian; Sonnenschein, Martin; Thali, Michael J; Aghayev, Emin; Yen, Kathrin; Dirnhofer, Richard; Vock, Peter

    2007-04-01

    Until August 2004 there were 106 forensic cases examined with postmortem multislice computed tomography (MSCT) and magnetic resonance (MR) imaging before traditional autopsy within the Virtopsy project. Intrahepatic gas (IHG) was a frequent finding in postmortem MSCT examinations. The aim of this study was to investigate its cause and significance. There were 84 virtopsy cases retrospectively investigated concerning the occurrence, location, and volume of IHG in postmortem MSCT imaging (1.25 mm collimation, 1.25 mm thickness). We assessed and noted the occurrence of intestinal distention, putrefaction, and systemic gas embolisms and the cause of death, possible open trauma, possible artificial respiration, and the postmortem interval. We investigated the relations between the findings using the contingency table (chi2 test) and the comparison of the postmortem intervals in both groups was performed using the t test in 79 nonputrefied corpses. IHG was found in 47 cases (59.5%). In five of the cases, the IHG was caused or influenced by putrefaction. Gas distribution within the liver of the remaining 42 cases was as follows: hepatic arteries in 21 cases, hepatic veins in 35 cases, and portal vein branches in 13 cases; among which combinations also occurred in 20 cases. The presence of IHG was strongly related to open trauma with systemic gas. Pulmonary barotrauma as occurring under artificial respiration or in drowning also caused IHG. Putrefaction did not seem to influence the occurrence of IHG until macroscopic signs of putrefaction were noticeable. IHG is a frequent finding in traumatic causes of death and requires a systemic gas embolism. Exceptions are putrefied or burned corpses. Common clinical causes such as necrotic bowel diseases appear rarely as a cause of IHG in our forensic case material.

  7. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    National Research Council Canada - National Science Library

    Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

    2014-01-01

    Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation...

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

    Directory of Open Access Journals (Sweden)

    Ramazan Akcan

    2010-06-01

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

  9. Mathematical modeling of inhalation exposure

    Science.gov (United States)

    Fiserova-Bergerova, V.

    1976-01-01

    The paper presents a mathematical model of inhalation exposure in which uptake, distribution and excretion are described by exponential functions, while rate constants are determined by tissue volumes, blood perfusion and by the solubility of vapors (partition coefficients). In the model, tissues are grouped into four pharmokinetic compartments. The model is used to study continuous and interrupted chronic exposures and is applied to the inhalation of Forane and methylene chloride.

  10. Exposure to inhalable, respirable, and ultrafine particles in welding fume.

    Science.gov (United States)

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

    2012-07-01

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

  11. Using helium-oxygen to improve regional deposition of inhaled particles: mechanical principles.

    Science.gov (United States)

    Katz, I; Pichelin, M; Montesantos, S; Majoral, C; Martin, A; Conway, J; Fleming, J; Venegas, J; Greenblatt, E; Caillibotte, G

    2014-04-01

    Helium-oxygen has been used for decades as a respiratory therapy conjointly with aerosols. It has also been shown under some conditions to be a means to provide more peripheral, deeper, particle deposition for inhalation therapies. Furthermore, we can also consider deposition along parallel paths that are quite different, especially in a heterogeneous pathological lung. It is in this context that it is hypothesized that helium-oxygen can improve regional deposition, leading to more homogeneous deposition by increasing deposition in ventilation-deficient lung regions. Analytical models of inertial impaction, sedimentation, and diffusion are examined to illustrate the importance of gas property values on deposition distribution through both fluid mechanics- and particle mechanics-based mechanisms. Also considered are in vitro results from a bench model for a heterogeneously obstructed lung. In vivo results from three-dimensional (3D) imaging techniques provide visual examples of changes in particle deposition patterns in asthmatics that are further analyzed using computational fluid dynamics (CFD). Based on analytical modeling, it is shown that deeper particle deposition is expected when breathing helium-oxygen, as compared with breathing air. A bench model has shown that more homogeneous ventilation distribution is possible breathing helium-oxygen in the presence of heterogeneous obstructions representative of central airway obstructions. 3D imaging of asthmatics has confirmed that aerosol delivery with a helium-oxygen carrier gas results in deeper and more homogeneous deposition distributions. CFD results are consistent with the in vivo imaging and suggest that the mechanics of gas particle interaction are the source of the differences seen in deposition patterns. However, intersubject variability in response to breathing helium-oxygen is expected, and an example of a nonresponder is shown where regional deposition is not significantly changed.

  12. Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

    Directory of Open Access Journals (Sweden)

    Pierre Ernst

    1998-01-01

    Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

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

    OpenAIRE

    Yi-fan LIU; Hong-wei TANG; Xiao-li WU; Yin-jing XIE; Hong-rui ZHANG; Jin-yan DUAN; Dai-jun XIANG; Xiao-mei LAN; Mian-yang LI; Cheng-bin WANG; Deng-qing LI

    2013-01-01

    Objective To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC) group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6). The arterial blood gas, wet to dry weight ratio (W/D) of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (...

  14. An advanced protocol-driven transition from parenteral prostanoids to inhaled trepostinil in pulmonary arterial hypertension

    OpenAIRE

    Oudiz, Ronald; Agarwal, Manyoo; Rischard, Franz; De Marco, Teresa

    2016-01-01

    Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids—such as catheter-related infections and intolerable adverse effects—may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients...

  15. Inhalant abuse: An exploratory study

    Directory of Open Access Journals (Sweden)

    Rohit Verma

    2011-01-01

    Full Text Available Background: Inhalants are being abused by large numbers of people throughout the world, particularly children and adolescents. It is also an often overlooked form of ubstance abuse in adolescents. Aims: The current study explored the inhalant abuse among adolescents seeking treatment from a tertiary care drug de-addiction clinic. Settings and Design: The study was conducted at a tertiary level multispecialty hospital. Materials and Methods: The current study was a chart review of the cases with inhalant abuse/dependence presenting to the clinic over a 1-year period. All the treatment records of the de-addiction clinic were reviewed, and information was gathered regarding patients with inhalant abuse/dependence. Statistical Analysis: Descriptive statistics with frequency distribution was carried out by using SPSS version 10.0. Results: The mean age of the subjects was 16.24 years (SD±1.9 years; range 12-18 years. Twenty-two percent of the subjects were illiterate. Forty percent of the adolescents had a family history of alcohol use problems and 48% that of tobacco use. The mean age of the initiation of inhalant use was 11.6 years (SD±2.17 years. It varied from 9 to 18 years. Forty percent of the adolescents had made a previous abstinence attempt. Conclusions: The findings provide important information on an underresearched area in psychiatry.

  16. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share ... to follow along with the correct way to use your metered dose inhaler. Print the step-by- ...

  17. Inhalant Abuse: Is Your Child at Risk?

    Science.gov (United States)

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

  18. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a spacer [ PDF - 377 KB] Your browser does not support iframes Cómo usar un inhalador de dosis fija ...

  19. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... metered dose inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a spacer [ PDF - 377 KB] Your browser does not support iframes Cómo usar un inhalador de ...

  20. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

    DEFF Research Database (Denmark)

    Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

    2017-01-01

    Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...

  1. Inhalation Therapy in Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Dilaver Tas

    2012-04-01

    Full Text Available Inhaled drug therapy in respiratory critical care units is an important treatment choice. İnhalation therapy has been in use since beginning of 1900%u2019s with the production of first liquid spray (atomiser. Today, there are numerous drugs given by inhalation. In this review, inhalational drugs and characteristics of inhalation therapy during invasive and noninvasive mechanical ventilation is described.

  2. Impact of inhalation therapy on oral health

    OpenAIRE

    Navneet Godara; Ramya Godara; Megha Khullar

    2011-01-01

    Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Beta-2 agonists, anticholinergic bronchodilators, inhaled corticosteroids, and sodium cromoglycate are often used alone or in combination in an inhaled form. Studies have shown that inhaled drugs used in the treatment have some adverse effects on the oral health based on their dosage, frequency, and duration of use. Several oral...

  3. Do misconceptions hinder effective inhalation therapy with dry powder inhalers?

    NARCIS (Netherlands)

    De Boer, A.H.; Hagedoorn, P.H.; Frijlink, H.W.F.

    Purpose: It is widely believed that high resistance dry powder inhalers (DPI's) can not be operated adequately by patients with reduced vital capacity and that a constant lung deposition requires a flow rate independent fine particle output (FPF). These beliefs may result in incorrect use and

  4. Inhalable drugs for systemic therapy.

    Science.gov (United States)

    Corkery, K

    2000-07-01

    Although oral and injectable drug formulations still dominate the market, interest in pulmonary delivery has been rising steadily. Given patients' desire for an alternative to injections, and recent advances in aerosol science and pulmonary medicine, the potential for improved disease management outcomes by using aerosols for systemic drug delivery should lead the way for a shift to inhalables.

  5. Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

    DEFF Research Database (Denmark)

    Sørli, Jorid Birkelund; Huang, Yishi; Da Silva, Emilie

    2018-01-01

    numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21...... the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large...... impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if they inhibited LS function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e. the in vitro method predicted...

  6. Validation of a general in vitro approach for prediction of total lung deposition in healthy adults for pharmaceutical inhalation products.

    Science.gov (United States)

    Olsson, Bo; Borgström, Lars; Lundbäck, Hans; Svensson, Mårten

    2013-12-01

    A validated method to predict lung deposition for inhaled medication from in vitro data is lacking in spite of many attempts to correlate in vitro and in vivo outcomes. By using an in vivo-like in vitro setup and analyzing inhalers from the same batches, both in vitro and in vivo, we wanted to create a situation where information from the in vitro and in vivo outcomes could be analyzed at the same time. Nine inhalation products containing either budesonide or AZD4818 were evaluated. These comprised two pressurized metered dose inhalers (pMDIs), a pMDI plus a spacer, four dry powder inhalers, and two dosimetric nebulizers. In vitro, an in vivo-like setup consisting of anatomically correct inlet throats were linked to a flow system that could replay actual inhalation flow profiles through the throat to a filter or to an impactor. In vivo, total lung deposition was measured in healthy adults by pharmacokinetic methods. We could show that the amount of drug escaping filtration in a realistic throat model under realistic delivery conditions predicts the typical total lung deposition in trained healthy adult subjects in the absence of significant exhaled mass. We could further show that by using combinations of throat models and flow profiles that represent realistic deviations from the typical case, variations in ex-cast deposition reflect between-subject variation in lung deposition. Further, we have demonstrated that ex-cast deposition collected either by a simple filter or by a cascade impactor operated at a fixed flow rate using a mixing inlet, to accommodate a variable flow profile through the inhaler, predicts equally well the lung deposited dose. Additionally, the ex-cast particle size distribution measured by this method may be relevant for predicting exhaled fraction and regional lung deposition by computational models.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Experimental observations of dry powder inhaler dose fluidisation.

    Science.gov (United States)

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

    2008-06-24

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

  10. Impact of inhalation therapy on oral health

    Directory of Open Access Journals (Sweden)

    Navneet Godara

    2011-01-01

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

  11. Impact of inhalation therapy on oral health.

    Science.gov (United States)

    Godara, Navneet; Godara, Ramya; Khullar, Megha

    2011-10-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  13. Excipient-API interactions in dry powder inhalers

    Directory of Open Access Journals (Sweden)

    Shireesh Apte

    2012-12-01

    Full Text Available There remains a paucity of predictive models to evaluate the suitability of excipients or excipient mixtures for dry powder inhalers because a large number of interdependent variables affect both formulation and inhaler performance. The problem is compounded by empirical studies that are performed under different experimental conditions which make data comparison difficult. An easily calculable molecular parameter, the Parachor, relates structural constants to surface tension. When applied in conjunction with results obtained from inverse gas chromatography, the Parachor can be used to calculate adhesive and cohesive surface energies between excipients and active pharmaceutical ingredients. Values calculated from the Parachor are consistent with qualitative hypotheses and agree reasonably well with published quantitative results. The ability to both achieve and predict the free particle fraction from Parachor derived surface energy data represents a new paradigm worthy of further perusal.

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

    Directory of Open Access Journals (Sweden)

    Yi-fan LIU

    2013-09-01

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

  15. Xenon-enhanced dual-energy CT of patients with asthma: dynamic ventilation changes after methacholine and salbutamol inhalation.

    Science.gov (United States)

    Kim, Won Wha; Lee, Chang Hyun; Goo, Jin Mo; Park, Sang Joon; Kim, Jong Hyo; Park, Eun-Ah; Cho, Sang-Heon

    2012-11-01

    The purpose of this study was to evaluate the use of xenon-enhanced dual-energy CT of the chest to assess ventilation changes after methacholine and salbutamol inhalation in subjects with asthma and healthy subjects. Twenty-five subjects with asthma and 10 healthy subjects underwent three-phase (basal, after methacholine inhalation, after salbutamol inhalation) xenon-enhanced chest CT. Each phase was composed of wash-in and washout scans. For visual analysis, two radiologists evaluated ventilation defects and gas trapping lobe by lobe on a 10-point scale. Total ventilation defect and gas trapping scores were calculated by adding ventilation defect and gas trapping scores. Xenon and total lung volume were quantified automatically. Total xenon concentration index was calculated as total xenon concentration divided by lung volume. Repeated measures analysis of variance and Student t test were used for comparisons of total ventilation defect score, total gas trapping score, and total xenon concentration index between the two groups. The Friedman test was used for within-group analysis. In the basal state, subjects with asthma had a higher total ventilation defect score (p = 0.004) and higher total gas trapping score (p = 0.05) than did healthy subjects. On washout images, total ventilation defect score, total gas trapping score, and total xenon concentration index after methacholine and salbutamol inhalation were statistically different between the two groups (p xenon concentration index on wash-in images was not significantly different between the two groups. In within-group analysis, total ventilation defect score and total gas trapping score in subjects with asthma and total ventilation defect score in healthy subjects increased significantly after methacholine inhalation and decreased significantly after salbutamol inhalation (p Xenon-enhanced chest CT may be a useful technique for visualizing dynamic changes in airflow in response to methacholine and salbutamol

  16. Inhalation therapy in mechanical ventilation

    Science.gov (United States)

    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

  17. Inhalation therapy in mechanical ventilation.

    Science.gov (United States)

    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.

  18. Passive inhalation of cannabis smoke

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-09-01

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

  19. Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic (PBPK) modeling for in vivo inhalation gas uptake data exposure in female B6C3F1 mice *

    Science.gov (United States)

    Dichloromethane (DCM, methylene chloride) is a lipophilic volatile compound readily absorbed and then metabolized to several metabolites that may lead to chronic toxicity in different target organs. Physiologically based pharmacokinetic (PBPK) models are useful tools used for cal...

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

    Science.gov (United States)

    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.

  1. Inhalation Injury: Pathophysiology, Diagnosis, and Treatment.

    Science.gov (United States)

    Jones, Samuel W; Williams, Felicia N; Cairns, Bruce A; Cartotto, Robert

    2017-07-01

    The classic determinants of mortality from severe burn injury are age, size of injury, delays of resuscitation, and the presence of inhalation injury. Of the major determinants of mortality, inhalation injury remains one of the most challenging injuries for burn care providers. Patients with inhalation injury are at increased risk for pneumonia (the leading cause of death) and multisystem organ failure. There is no consensus among leading burn care centers in the management of inhalation injury. This article outlines the current treatment algorithms and the evidence of their efficacy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Helium induces preconditioning in human endothelium in vivo.

    Science.gov (United States)

    Smit, Kirsten F; Oei, Gezina T M L; Brevoord, Daniel; Stroes, Erik S; Nieuwland, Rienk; Schlack, Wolfgang S; Hollmann, Markus W; Weber, Nina C; Preckel, Benedikt

    2013-01-01

    Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min. Endothelium-dependent and endothelium-independent responses were measured after cumulative dose-response infusion of acetylcholine and sodium nitroprusside, respectively, at baseline and after 15 min of reperfusion using strain-gauge, venous occlusion plethysmography. Helium preconditioning was applied by inhalation of helium (79% helium, 21% oxygen) either 15 min (helium early preconditioning [He-EPC]) or 24 h before I/R (helium late preconditioning). Additional measurements of He-EPC were done after blockade of endothelial nitric oxide synthase. Plasma levels of cytokines, adhesion molecules, and cell-derived microparticles were determined. Forearm I/R attenuated endothelium-dependent vasodilation (acetylcholine) with unaltered endothelium-independent response (sodium nitroprusside). Both He-EPC and helium late preconditioning attenuated I/R-induced endothelial dysfunction (max increase in forearm blood flow in response to acetylcholine after I/R was 180 ± 24% [mean ± SEM] without preconditioning, 573 ± 140% after He-EPC, and 290 ± 32% after helium late preconditioning). Protection of helium was comparable to ischemic preconditioning (max forearm blood flow 436 ± 38%) and was not abolished after endothelial nitric oxide synthase blockade. He-EPC did not affect plasma levels of cytokines, adhesion molecules, or microparticles. Helium is a nonanesthetic, nontoxic gas without hemodynamic side effects, which induces early and late preconditioning of human endothelium in vivo. Further studies have to investigate whether helium may be an instrument to induce endothelial preconditioning in patients with cardiovascular risk factors.

  3. Regional cerebral blood flow by radioxenon-113 inhalation and dynamic emission tomography

    DEFF Research Database (Denmark)

    Lassen, N A; Henriksen, L; Paulson, O B

    1981-01-01

    A rapidly rotating single photon tomograph is described for atraumatic and three-dimensional measurements of rCBF in ml/100 g/min. The instrument has a high sensitivity permitting the recording of the uptake and washout of xenon-133 from the human brain during and after inhalation of the gas...

  4. A portable inhalation system for personal exposure to ozone.

    Science.gov (United States)

    Asplund, P T; Ben-Jebria, A; Ultman, J S

    1996-01-01

    A low-cost portable inhalation system was developed for exposing an individual subject to 60-600 parts per billion of ozone in a 30-l clear-plastic head dome. The inhalation system had the following novel features: a canister vacuum cleaner that supplied room air without the need for precleaning or humidification; a 7% oxygen-in-nitrogen feed to a commercial ultraviolet ozonator that avoided an excess production of ozone; a compact inline mixer that assured homogeneous mixing of the 200-300 liters per minute room air supply with the 0.5-1.0 liters per minute of ozonated gas flow, positioning of gas inlet and exhaust hoses on the head dome that provided fresh gas delivery in the vicinity of the mouth; a quick-disconnect neck seal that allowed rapid donning of the head dome by the subject, and mounting of most system components on a small mobile cart. Temperature, humidity, and ozone and carbon dioxide concentrations were measured inside the dome while a subject exercised on a bicycle ergometer. An air flow of 200 liters per minute between rest and light exercise created a suitable microenvironment in the dome. During moderate and heavy exercise, however, a higher flow of 300 liters per minute should be used to suppress the build-up of carbon dioxide and humidity.

  5. The Pathophysiology of Nitrogen Dioxide During Inhaled Nitric Oxide Therapy.

    Science.gov (United States)

    Petit, Priscilla C; Fine, David H; Vásquez, Gregory B; Gamero, Lucas; Slaughter, Mark S; Dasse, Kurt A

    Administration of inhaled nitric oxide (NO) with the existing compressed gas delivery systems is associated with unavoidable codelivery of nitrogen dioxide (NO2), an unwanted toxic contaminant that forms when mixed with oxygen. The NO2 is generated when NO is diluted with O2-enriched air before delivery to the patient. When NO2 is inhaled by the patient, it oxidizes protective antioxidants within the epithelial lining fluid (ELF) and triggers extracellular damage in the airways. The reaction of NO2 within the ELF triggers oxidative stress (OS), possibly leading to edema, bronchoconstriction, and a reduced forced expiratory volume in 1 second. Nitrogen dioxide has been shown to have deleterious effects on the airways of high-risk patients including neonates, patients with respiratory and heart failure, and the elderly. Minimizing co-delivery of NO2 for the next generation delivery systems will be a necessity to fully optimize the pulmonary perfusion of NO because of vasodilation, whereas minimizing the negative ventilatory and histopathological effects of NO2 exposure during inhaled NO therapy.

  6. Physiological daily inhalation rates for health risk assessment in overweight/obese children, adults, and elderly.

    Science.gov (United States)

    Brochu, Pierre; Bouchard, Michèle; Haddad, Sami

    2014-03-01

    Physiological daily inhalation rates reported in our previous study for normal-weight subjects 2.6-96 years old were compared to inhalation data determined in free-living overweight/obese individuals (n = 661) aged 5-96 years. Inhalation rates were also calculated in normal-weight (n = 408), overweight (n = 225), and obese classes 1, 2, and 3 adults (n = 134) aged 20-96 years. These inhalation values were based on published indirect calorimetry measurements (n = 1,069) and disappearance rates of oral doses of water isotopes (i.e., (2)H2 O and H2 (18)O) monitored by gas isotope ratio mass spectrometry usually in urine samples for an aggregate period of over 16,000 days. Ventilatory equivalents for overweight/obese subjects at rest and during their aggregate daytime activities (28.99 ± 6.03 L to 34.82 ± 8.22 L of air inhaled/L of oxygen consumed; mean ± SD) were determined and used for calculations of inhalation rates. The interindividual variability factor calculated as the ratio of the highest 99th percentile to the lowest 1st percentile of daily inhalation rates is higher for absolute data expressed in m3 /day (26.7) compared to those of data in m3/kg-day (12.2) and m3/m2-day (5.9). Higher absolute rates generally found in overweight/obese individuals compared to their normal-weight counterparts suggest higher intakes of air pollutants (in μg/day) for the former compared to the latter during identical exposure concentrations and conditions. Highest absolute mean (24.57 m3/day) and 99th percentile (55.55 m3 /day) values were found in obese class 2 adults. They inhale on average 8.21 m3 more air per day than normal-weight adults. © 2013 Society for Risk Analysis.

  7. An advanced protocol-driven transition from parenteral prostanoids to inhaled trepostinil in pulmonary arterial hypertension.

    Science.gov (United States)

    Oudiz, Ronald; Agarwal, Manyoo; Rischard, Franz; De Marco, Teresa

    2016-12-01

    Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids-such as catheter-related infections and intolerable adverse effects-may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil. Rigid inclusion criteria were used, including parenteral prostanoid dose < 30 ng/kg/min, New York Heart Association functional class (FC) < 3, and pulmonary vascular resistance (PVR) < 6 Wood units. Of the 9 patients meeting initial inclusion criteria, 3 were excluded. In the remaining patients, the parenteral prostanoid was reduced and the inhaled prostanoid was increased over 24-36 hours with continuous hemodynamic monitoring. Exercise capacity and FC were measured at baseline and weeks 1, 4, and 12. All patients were successfully weaned from parenteral prostanoids. An acute PVR decrease was seen with most inhaled prostanoid doses, but PVR varied throughout the transition. Patients tolerated inhaled prostanoids for 9-12 breaths 4 times a day with no treatment-limiting adverse events. At week 12, FC was unchanged, and all patients continued to receive inhaled prostanoids without serious adverse events or additional PAH therapy. In 5 of 6 patients, 6-minute walk distance and peak [Formula: see text] were within 10% of baseline. Using a strict transition protocol and rigid patient selection criteria, the parenteral prostanoid to inhaled prostanoid transition appeared safe and well tolerated and did not result in clinical deterioration over 12 weeks. Hemodynamic variability noted acutely during transition in our study did not adversely affect successful transition. (Trial registration: Clinical

  8. An advanced protocol-driven transition from parenteral prostanoids to inhaled trepostinil in pulmonary arterial hypertension

    Science.gov (United States)

    Agarwal, Manyoo; Rischard, Franz; De Marco, Teresa

    2016-01-01

    Abstract Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids—such as catheter-related infections and intolerable adverse effects—may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil. Rigid inclusion criteria were used, including parenteral prostanoid dose < 30 ng/kg/min, New York Heart Association functional class (FC) < 3, and pulmonary vascular resistance (PVR) < 6 Wood units. Of the 9 patients meeting initial inclusion criteria, 3 were excluded. In the remaining patients, the parenteral prostanoid was reduced and the inhaled prostanoid was increased over 24–36 hours with continuous hemodynamic monitoring. Exercise capacity and FC were measured at baseline and weeks 1, 4, and 12. All patients were successfully weaned from parenteral prostanoids. An acute PVR decrease was seen with most inhaled prostanoid doses, but PVR varied throughout the transition. Patients tolerated inhaled prostanoids for 9–12 breaths 4 times a day with no treatment-limiting adverse events. At week 12, FC was unchanged, and all patients continued to receive inhaled prostanoids without serious adverse events or additional PAH therapy. In 5 of 6 patients, 6-minute walk distance and peak V˙O2 were within 10% of baseline. Using a strict transition protocol and rigid patient selection criteria, the parenteral prostanoid to inhaled prostanoid transition appeared safe and well tolerated and did not result in clinical deterioration over 12 weeks. Hemodynamic variability noted acutely during transition in our study did not adversely affect successful transition. (Trial registration: Clinical

  9. Subchronic inhalation toxicity of gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Chung Yong

    2011-05-01

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

  10. Acute fatal occupational cadmium poisoning by inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, K.; Ueda, M.; Kikuchi, H.; Hattori, H.; Hiraoka, Y.

    1983-01-01

    A 43-year-old male smelter was admitted to a hospital on account of severe dyspnea about 2 days after exposure to brownish-yellow smoke produced by melting of ''copper'' scrap. On admission pronounced hypoxemia was revealed, and an oxygen-enriched gas was administered after intubation. Although inspired oxygen concentration was gradually increased, hypoxemia progressed and he died on day 11 in hospital. The principal autopsy finding was chiefly confined to the lungs. Both lungs were heavy (the left weighing 1,470 g; the right 1,710 g) and firm to the touch. Histologically, no normal alveoli were found throughout the entire lung. Some alveolar spaces were occupied by pneumocytes, others by organized exudate with fibrosis. Interstitial fibrosis was present. Patchy areas of inflammatory cell infiltrations as well as intra-alveolar hemorrhages were observed. On the basis of the above findings a diagnosis of diffuse alveolar damage was made. Based on the available evidence (presence of cadmium in the ''copper'' scrap, feature of the smoke, clinical signs with latent time, and high cadmium concentration of the lung), the diffuse alveolar damage was considered to have been caused by inhaled cadmium. The pulmonary change of the present case was more advanced in pathologic stage in comparison with those reported in the literature.

  11. Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer

    DEFF Research Database (Denmark)

    Nielsen, K G; Skov, M; Klug, B

    1997-01-01

    The output and size distribution of aerosols from dry powder inhalers are dependent on the flow rate through the device. Therefore, in an in vivo study, we examined the flow-dependency of the effect of formoterol when delivered from a dry powder inhaler, the Aerolizer, in a flow range relevant...... a flow-dependent effect of formoterol dry powder inhaled from the Aerolizer, within the range of inspiratory flow rate obtainable by school-children. This questions its applicability in children with asthma....... to schoolchildren. In a preliminary study comprising 126 asthmatic children aged 3-10 yrs, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer was determined. Mean PIF was 104 L.min-1 and all children aged > 5 yrs performed a PIF > 60 L.min-1. Sixteen children aged 8-15 yrs...

  12. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... iframes Using a metered dose inhaler (inhaler in mouth) [PDF - 370 KB] Your browser does not support iframes Cómo usar un inhalador de dosis fija (inhalador de boca) [PDF - 276 KB] Follow @CDCasthma on Twitter to learn more about helping people with asthma live healthier ...

  13. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... keep them with your Asthma Action Plan. Using a metered dose inhaler with a spacer Your browser does not support iframes Using ... dosis fija con espaciador [PDF - 343 KB] Using a metered dose inhaler one to two inches from ...

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Evaluation Roadblocks 1A. Focus On: Walking Through the Steps and Standards 2. Getting Started 3. Describing and Focusing 3A. Focus ... your metered dose inhaler. Print the step-by-step instructions and keep them with your ... dose inhaler one to two inches from mouth Your browser does not support ...

  15. Inhalant Abuse: A Call for Attention.

    Science.gov (United States)

    Ballard, Mary B.

    1998-01-01

    The percentage of youth inhaling volatile substances is on the rise in the United States. Professional literature has been critical of the helping professions for not doing enough to address this problem adequately. This article attempts to heighten the awareness of the mental health profession by defining inhalant abuse, its consequences, and…

  16. [Inhalation therapy in children with asthma].

    Science.gov (United States)

    de Jongste, J C; van Essen-Zandvliet, E E; Brackel, H J; Kerrebijn, K F

    1990-02-01

    Inhalation therapy for childhood asthma is safe and effective. It has the advantages of a low dose, a rapid effect and a wide therapeutic range. For the majority of children the available medications make it possible now to treat asthma optimally, provided that special care is taken to select the appropriate inhalation devices, and repeated practical instructions are given.

  17. Inhaler devices - from theory to practice

    DEFF Research Database (Denmark)

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

    2013-01-01

    This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...

  18. Adolescent Inhalant Use and Perceived Stress.

    Science.gov (United States)

    Mitic, Wayne R.; And Others

    1987-01-01

    Surveyed 1,684 secondary school students on stress and inhalant use. Classified inhalent users as abstainers, experimental, and regular users. Male abstainers exhibited lower mean stress scores than did males in other groups; female abstainers exhibited lower mean scores than did regular users but did not differ from experimental users. Suggests…

  19. Not all asthma inhalers are the same: factors to consider when prescribing an inhaler.

    Science.gov (United States)

    Chrystyn, Henry; Price, David

    2009-12-01

    National and international asthma guidelines stress that before making changes to patients' therapy their compliance and inhaler technique should be checked. This review addresses these issues and highlights the differences between inhalers in terms of inhaler technique, individual ability/competence, and ease of use. The advantages and disadvantages of metered-dose inhalers (MDIs) and dry powder inhalers (DPIs) are presented. The reformulation of beclometasone MDIs is discussed since there has been some confusion over prescribing and Regulatory Authorities have recommended that these should be prescribed by brand name and not generically. This review should provide prescribers with an update to help them appreciate the differences between inhalers thereby optimising each patient's inhaled treatment.

  20. Effect of Budesonide by metered dose inhaler with or without spacer & dry powder inhaler on Lung Function

    OpenAIRE

    Dilshad Ali Rizvi; Mohammad Tariq Salman; Joydeep Sircar; Ali Ahmad

    2013-01-01

    Aims & objective-To compare the efficacy of Budesonide delivered by metered dose inhaler, metered dose inhaler with spacer and dry powder inhaler on the lung function test parameters. Materials and Methods: This prospective study was undertaken to assess the effect of budesonide administered from fifty patients of chronic stable bronchial asthma were budesonide(400mcg) by metered dose inhaler, metered dose inhaler with spacer and by dry powder inhaler at day 14, 21 and 28 after enrolment ...

  1. Allergy to inhaled egg material.

    Science.gov (United States)

    Edwards, J H; McConnochie, K; Trotman, D M; Collins, G; Saunders, M J; Latham, S M

    1983-09-01

    The use of a spray system to coat meat rolls with egg solution resulted in the development of asthmatic type symptoms in eight of thirteen workers exposed to the spray. Symptoms were severe in five workers, less severe in two, and one worker experienced vague symptoms. Even though precipitins were present in nine of the workers there were no pyrexial episodes nor influenza-like symptoms occurring some hours after inhaling the egg material to suggest extrinsic allergic alveolitis. All sera with precipitins reacted against an antigen in egg yolk, two sera only to this antigen but no precipitins to ovalbumin were detected. Lung function, X-ray and haematology provided no evidence that the inhalation of egg had lasting detrimental effects. There was no correlation between clinical response, skin testing, IgE levels and precipitins, hence, for each individual none of these parameters is predictive. However, collectively the results show sensitization and this has been confirmed by lack of symptoms when a different method of coating the pastry was adopted.

  2. Inhalant Dependence and its Medical Consequences

    Directory of Open Access Journals (Sweden)

    Mehmet Hamid Boztaş

    2010-12-01

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

  3. The Ozone Layer and Metered Dose Inhalers

    Directory of Open Access Journals (Sweden)

    Louis-Philippe Boulet

    1998-01-01

    Full Text Available The stratospheric ozone layer plays a crucial role in protecting living organisms against ultraviolet radiation. Chlorofluorocarbons (CFC contained in metered-dose inhalers (MDIs contribute to ozone depletion and in accordance with the Montreal Protocol on Substances That Deplete the Ozone Layer established 10 years ago, phase-out strageies have been developed worldwide for this category of agents. Alternatives to CFC-containing inhalers have been developed, such as powder inhalers and those using hydrofluoroalkanes (HFAs as propellants, which have been shown to be as safe and effective as CFC-containing inhalers and even offer interesting advantages over older inhalers. The transition to non-CFC MDIs requires a major effort to make the new products available and to ensure adequate comparision with the previous ones. It also requires a harmonization of actions taken by industry, government, licencing bodies and patients or health professional associations to ensure adequate information and education to the public and respiratory care providers.

  4. Inhalants

    Science.gov (United States)

    ... Trends Nationwide Trends Prevention and Treatment Lessons from Prevention Research Substance Abuse in the Military Treatment Approaches for Drug Addiction Get this Publication Español PDF (750KB) Cite this ...

  5. Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA? Dry Powder Inhaler

    OpenAIRE

    Prime, David; de Backer, Wilfried; Hamilton, Melanie; Cahn, Anthony; Preece, Andrew; Kelleher, Dennis; Baines, Amanda; Moore, Alison; Brealey, Noushin; Moynihan, Jackie

    2015-01-01

    Abstract Background: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. Methods: Healthy subjects (n?=?15), patients with mild, moderate, or severe asthma (n?=?45), and patients with ...

  6. Suffocation caused by plastic wrap covering the face combined with nitrous oxide inhalation

    DEFF Research Database (Denmark)

    Leth, Peter Mygind; Astrup, Birgitte Schmidt

    2017-01-01

    as laughing gas, has a euphoric effect and is used as a recreational inhalant drug that can be purchased legally. Deaths caused by recreational nitrous oxide abuse are rare but may occur if used in combination with a plastic bag over the head. This is the first report of suicide by suffocation by external...... with nitrous oxide inhalation, is presented. The case was reviewed based on police, autopsy and hospital reports. A PubMed search for scientific literature related to nitrous oxide abuse and suicide by suffocation was performed and our findings discussed in relation to the scientific literature found...

  7. Inhalable bioresponsive chitosan microspheres of doxorubicin and soluble curcumin augmented drug delivery in lung cancer cells.

    Science.gov (United States)

    Jyoti, Kiran; Pandey, Ravi Shankar; Kush, Preeti; Kaushik, Dinesh; Jain, Upendra Kumar; Madan, Jitender

    2017-05-01

    In present investigation, doxorubicin (Dox) and soluble curcumin (Cur-2-HP-β-CD-complex) combination was simultaneously loaded in inhalable bioresponsive chitosan microspheres (Dox/Cur-2-HP-β-CD-complex-elastin-CMs) bearing a substrate-stimuli, elastin. The mean particle size and mean aerodynamic diameter of inhalable bioresponsive microspheres displayed noteworthy differences after incorporation of elastin. Moreover, combination of Dox and soluble curcumin was molecularly dispersed in microspheres matrix as substantiated by a range of spectral techniques. Inhalable bioresponsive microspheres released astonishingly higher amount of Dox in presence of elastase enzyme at pH∼5.5 in comparison to pH∼7.4. However, the release of soluble curcumin from tailored bioresponsive microspheres in presence of elastase enzyme was independent of pH. Consistently, inhalable bioresponsive microspheres exhibited outstandingly lower IC 50 of 3.4-μM in comparison to 6.5-μM of inhalable drug loaded microspheres (Dox/Cur-2-HP-β-CD-complex-CMs) bearing no elastin, against A549, non-small cell lung cancer cells. The superior therapeutic profile of inhalable bioresponsive microspheres may be attributed to enhanced drug release and consequently augmented drug exposure to A549 cells expressing elastase enzyme. In this way, stimuli triggered drug release from tailored inhalable bioresponsive microspheres boosted the phenomena of apoptosis in A549 cells. In conclusion, Dox/Cur-2-HP-β-CD-complex-elastin-CMs warrant further in-vivo tumor regression study to prove its therapeutic efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

  9. Laryngeal sequelae due to accidental inhalation of anhydrous ammonia

    Directory of Open Access Journals (Sweden)

    Cruz, Walter Paiva

    2009-03-01

    Full Text Available Introduction: Anhydrous Ammonia (AA is a caustic compound commonly used in the industry that can cause burns, even with brief contact. As with other alkali burns, the early washing to remove the AA from burnt areas is crucial to limit tissue damage. The concentration of toxic agent and duration of its contact determine the degree of skin and mucosa destruction. A tanker truck carrying AA (NH3 fell off a highway, and released a dense cloud of AA gas. Fifty-four people inhaled the gas and after ninety days, three people were still experiencing hoarseness and were examined. Case Report: We assessed three patients with laryngeal sequelae due to AA inhalation burn. We found a case of hyperemia and edema, one case of granuloma of the posterior third portion of the left vocal cord, and one case of vocal cord adhesion. Necropsy findings are commented both macroscopically and microscopically. The sequelae and the best treatments for them are discussed herein.

  10. Inhalation anaesthetics and climate change

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  11. Seat headrest-incorporated personalized ventilation: Thermal comfort and inhaled air quality

    DEFF Research Database (Denmark)

    Melikov, Arsen Krikor; Ivanova, T.; Stefanova, G.

    2012-01-01

    inhaled by the manikin was measured and used to assess the clean air supply efficiency of the SHPV. The response of 35 subjects was collected to examine thermal comfort with the SHPV. The subjects participated in 3 experiments at personalized air temperature and room air temperature of 22/20 °C, 23/23 °C......The performance of personalized ventilation with seat headrest-mounted air supply terminal devices (ATD), named seat headrest personalized ventilation (SHPV), was studied. Physical measurements using a breathing thermal manikin were taken to identify its ability to provide clean air to inhalation...... depending on design, shape, size and positioning of the ATD, flow rate and temperature of personalized air, room temperature, clothing thermal insulation of the manikin, etc. Tracer gas was mixed with the room air. The air supplied by the SHPV was free of tracer gas. Tracer gas concentration in the air...

  12. The Effects of Inhaled β-Adrenergic Agonists in Transient Tachypnea of the Newborn

    Directory of Open Access Journals (Sweden)

    Esengul Keleş MD

    2016-05-01

    Full Text Available Aim. To investigate the efficacy of an inhaled β-adrenergic agonists in transient tachypnea of the newborn (TTN. Method. We retrospectively analyzed a cohort of 51 term infants (Group 1 and 37 term infants (Group 2 monitored in the newborn intensive care unit diagnosed with TTN. Infants in Group 1 received humidified oxygen alone, and infants in Group 2 were administered the inhaled β-2 agonist plus humidified oxygen. Results. TTN clinical respiratory assessment, respiratory rate, oxygen saturation values, need for supplemental oxygen therapy, blood gas PH, PO2, and duration of hospitalization were significantly improved in infants in Group 2 as compared with infants in Group 1 (P .05. Conclusion. Inhaled β-adrenergic agonist added to humidified oxygen was found to improve clinical and laboratory parameters. We believe that further studies should be conducted with larger groups to demonstrate the efficacy of β-2 agonists in TTN patients.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  14. Inhalation of Alcohol Vapor: Measurement and Implications.

    Science.gov (United States)

    MacLean, Robert Ross; Valentine, Gerald W; Jatlow, Peter I; Sofuoglu, Mehmet

    2017-02-01

    Decades of alcohol research have established the health risks and pharmacodynamic profile of oral alcohol consumption. Despite isolated periods of public health concern, comparatively less research has evaluated exposure to alcohol vapor. Inhaled alcohol initially bypasses first-pass metabolism and rapidly reaches the arterial circulation and the brain, suggesting that this route of administration may be associated with pharmacological effects that increase the risk of addiction. However, detailed reviews assessing the possible effects of inhaled alcohol in humans are lacking. A comprehensive, systematic literature review was conducted using Google Scholar and PubMed to examine manuscripts studying exposure to inhaled alcohol and measurement of biomarkers (biochemical or functional) associated with alcohol consumption in human participants. Twenty-one publications reported on alcohol inhalation. Fourteen studies examined inhalation of alcohol vapor associated with occupational exposure (e.g., hand sanitizer) in a variety of settings (e.g., naturalistic, laboratory). Six publications measured inhalation of alcohol in a controlled laboratory chamber, and 1 evaluated direct inhalation of an e-cigarette with ethanol-containing "e-liquid." Some studies have reported that inhalation of alcohol vapor results in measurable biomarkers of acute alcohol exposure, most notably ethyl glucuronide. Despite the lack of significantly elevated blood alcohol concentrations, the behavioral consequences and subjective effects associated with repeated use of devices capable of delivering alcohol vapor are yet to be determined. No studies have focused on vulnerable populations, such as adolescents or individuals with alcohol use disorder, who may be most at risk of problems associated with alcohol inhalation. Copyright © 2017 by the Research Society on Alcoholism.

  15. Toxicology Studies for Inhaled and Nasal Delivery.

    Science.gov (United States)

    Wolff, R K

    2015-08-03

    This review examines issues related to the toxicological testing of pharmaceuticals delivered by the inhalation or nasal route. The purpose of the toxicology studies is to conduct studies in animals that will aid the assessment of the safety of these agents delivered to patients. Inhalation toxicology studies present some unique issues because the dosing method differs from more standard administration methods such as oral or injection administration. Also, dose determination issues are more complex, particularly for inhalation administration since it is often difficult to determine the amount of material delivered to the lung both for patients and in animal toxicology studies.

  16. Synthesis and evaluation of inhaled [{sup 11}C]butane and intravenously injected [{sup 11}C]acetone as potential radiotracers for studying inhalant abuse

    Energy Technology Data Exchange (ETDEWEB)

    Gerasimov, Madina R. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ferrieri, Richard A. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Pareto, Deborah [Department of Nuclear Medicine and Functional Imaging, Functional Imaging, Berkeley National Laboratory, Berkeley, CA 94720 (United States); Logan, Jean [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)]. E-mail: logan@bnl.gov; Alexoff, David [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States); Ding Yushin [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2005-02-01

    The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of {sup 11}C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [{sup 11}C]toluene to include [{sup 11}C]acetone and [{sup 11}C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [{sup 11}C]toluene and [{sup 11}C]acetone were administered intravenously and [{sup 11}C]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [{sup 11}C]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane.

  17. Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler.

    Science.gov (United States)

    Buttini, Francesca; Pasquali, Irene; Brambilla, Gaetano; Copelli, Diego; Alberi, Massimiliano Dagli; Balducci, Anna Giulia; Bettini, Ruggero; Sisti, Viviana

    2016-03-01

    The aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances. The two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain. Breath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs. The multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL).

  18. Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and elimination in a piglet model.

    Science.gov (United States)

    Kretzschmar, Moritz; Kozian, Alf; Baumgardner, James E; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2016-01-01

    Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We hypothesized that pharmacokinetics of volatile anesthetics would be affected by bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of desflurane in both healthy state and during inhalational administration of methacholine (MCh) to double peak airway pressure were studied in a piglet model. In piglets, MCh administration by inhalation (100 μg/ml, n=6) increased respiratory resistance, impaired VA/Q distribution, increased shunt, and decreased paO2 in all animals. The uptake and elimination of desflurane in arterial blood was delayed by nebulization of MCh, as determined by Micropore Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation: 0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed both uptake and elimination of desflurane. These findings might be considered when administering inhalational anesthesia to asthmatic patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Pharmacokinetics and pharmacodynamics of moist inhalation epinephrine using a mobile inhaler

    OpenAIRE

    Breuer, C.; Wachall, B.; Gerbeth, K; Abdel-Tawab, M.; Fuhr, U

    2013-01-01

    Background Intramuscular (L-)epinephrine is used as self-medication for serious hypersensitivity reactions. Inhalative administration has the theoretical advantage of a more rapid absorption and better controllability. Objectives The current trial was conducted to explore pharmacokinetics and pharmacodynamics of two nebulized inhalative epinephrine doses (4?mg and 8?mg in aqueous solution) using a mobile pocket inhaler relative to intramuscular administration (0.3?mg) and placebo. Methods Thi...

  20. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Quick Links Asthma Action Plan America Breathing Easier [PDF – 1.1 MB] ASL Asthma Film Asthma Clinical ... Using a metered dose inhaler with a spacer [ PDF - 377 KB] Your browser does not support iframes ...

  1. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... physicians’ office Health care providers – Other Parents – Home Case Studies Open Airways for Schools Asthma Care Training ...

  2. Inhaled Corticosteroid Therapy Does Not Control Asthma

    Directory of Open Access Journals (Sweden)

    Robert L Cowie

    2004-01-01

    Full Text Available BACKGROUND: Randomized clinical trials demonstrate efficacy and show that inhaled corticosteroid therapy can control asthma, but details concerning their effectiveness in achieving this goal in the community are lacking.

  3. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by ... you to do and by avoiding things that can cause an attack. Watch a video to follow ...

  4. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler ... MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I view ...

  5. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most Recent ... Archive 2014 State or Territory Data Archive AsthmaStats Flu Vaccination among Adults with Current Asthma Flu Vaccination ...

  6. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler ... ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I view ...

  7. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine ...

  8. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook ... Guidelines Air Pollution & Respiratory Health File Formats Help: How do I view different file formats (PDF, DOC, ...

  9. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... supported by your browser. For this reason, some items on this page will be unavailable. For more information about this ... Plan Flu Shots Inhalers Data, Statistics, and Surveillance ...

  10. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack ...

  11. Inhalant Abuse: Is Your Child at Risk?

    Science.gov (United States)

    ... Medical Services. 2009;34:42. Drug prevention 4 teens. Drug Enforcement Administration. http://www.dea.gov/pr/multimedia- ... 4, 2014. Inhalants research report. National Institute on Drug Abuse. ... . Mayo ...

  12. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Mixed Methods 5. Purpose Informs Design Other Evaluation Resources Multimedia ... USA.gov Top

  13. Know How to Use Your Asthma Inhaler

    Medline Plus

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

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... page: About CDC.gov . Asthma Learn How to Control Asthma Asthma and Severe Weather Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  15. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet ... your doctor or other medical professional tells you to do and by avoiding things that can cause ...

  16. Health risks associated with inhaled nasal toxicants

    NARCIS (Netherlands)

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

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

  17. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Work-related Asthma NCHS Asthma FastStats Survey Questions Resources for Health Professionals and Schools Healthcare Professionals Public ...

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

    Science.gov (United States)

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

    2017-01-01

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

  19. In vitro dry powder inhaler formulation performance considerations.

    Science.gov (United States)

    Ziffels, Susanne; Bemelmans, Norman L; Durham, Phillip G; Hickey, Anthony J

    2015-02-10

    It has long been desired to match airflow conditions during formulation evaluation to those of relevance to lung deposition. In this context several strategies have been adopted involving sampling at different: flow rate (without consideration of flow conditions, e.g. shear, Reynolds number, work function); pressure drop (with and without consideration of flow conditions) and; flow rate and pressure drop. Performance testing has focused on the influence of these sampling conditions on delivered dose uniformity and aerodynamic particle size distribution. However, in order to be physiologically relevant it is also important to know when the drug was delivered with respect to initiation of airflow as variation in this parameter would influence lung deposition. A light obscuration method of detecting the dose delivered from a dry powder inhaler while sampling for aerodynamic particle size distributions (APSD) by inertial impaction has been developed. Four formulations of albuterol sulfate and budesonide in sieved and milled lactose, respectively, were dispersed and their rate of delivery monitored. The differences observed have the potential to impact the site of delivery in the lungs. The rate of delivery of drug is clearly an important companion measurement to delivered dose and APSD if the intent is to predict the similarity of in vivo performance of dry powder inhaler products. Copyright © 2014. Published by Elsevier B.V.

  20. ARDS following inhalation of hydrochloric acid.

    Science.gov (United States)

    Bansal, D P; Ambegaonkar, Rahul; Radhika, P; Sharma, Manish

    2011-02-01

    The clinical spectrum of Inhalation injury can range from mild cough to a devastating ARDS. We herewith present a patient who is a goldsmith by occupation and his work consists of dissolving gold in Hydrochloric acid. He had accidentally inhaled fumes of Hydrochloric acid and presented with cough and breathlessness, later on required mechanical ventilation for ARDS and improved. This highlights the importance of not to neglect mild symptoms like cough and dyspnea in such a scenario which may have some hidden catastrophe.

  1. Paradoxical conducting airway responses and heterogeneous regional ventilation after histamine inhalation in rabbit studied by synchrotron radiation CT.

    Science.gov (United States)

    Bayat, Sam; Porra, Liisa; Suhonen, Heikki; Suortti, Pekka; Sovijärvi, Anssi R A

    2009-06-01

    We studied both central conducting airway response and changes in the distribution of regional ventilation induced by inhaled histamine in healthy anesthetized and mechanically ventilated rabbit using a novel xenon-enhanced synchrotron radiation computed tomography (CT) imaging technique, K-edge subtraction imaging (KES). Images of specific ventilation were obtained using serial KES during xenon washin, in three axial lung slices, at baseline and twice after inhalation of histamine aerosol (50 or 125 mg/ml) in two groups of animals (n = 6 each). Histamine inhalation caused large clustered areas of poor ventilation, characterized by a drop in average specific ventilation (sV(m)), but an increase in sV(m) in the remaining lung zones indicating ventilation redistribution. Ventilation heterogeneity, estimated as coefficient of variation (CV) of sV(m) significantly increased following histamine inhalation. The area of ventilation defects and CV were significantly larger with the higher histamine dose. In conducting airways, histamine inhalation caused a heterogeneous airway response combining narrowing and dilatation in individual airways of different generations, with the probability for constriction increasing peripherally. This finding provides further in vivo evidence that airway reactivity in response to inhaled histamine is complex and that airway response may vary substantially with location within the bronchial tree.

  2. Age dependent systemic exposure to inhaled salbutamol

    DEFF Research Database (Denmark)

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

    2007-01-01

    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing ...... (95%CI) = 1.7 (1.3, 2.2)). CONCLUSIONS: For similar systemic exposure, dosing should be adjusted to age or size but not on a fixed microg kg(-1) basis, which may lead to unnecessary suboptimal dosing.......AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...... a dose on a microg kg(-1) basis caused reduced systemic exposure in young children (Y) compared with older children (O) (C(max-microg kg(-1)-adjusted) Y : O ratio (95%CI) = 0.55 (0.47, 0.65)) whereas a fixed nominal dose irrespective of age caused increased exposure in young children (C(max) Y : O ratio...

  3. Inhalational Monkeypox Virus Infection in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roy eBarnewall

    2012-09-01

    Full Text Available An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV, and a nonhuman primate (NHP inhalation monkeypox model was developed in cynomologus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD was for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 µm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 x 104 to 9.28 x 105 plaque forming units (pfu inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 x 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.

  4. Suffocation caused by plastic wrap covering the face combined with nitrous oxide inhalation.

    Science.gov (United States)

    Leth, Peter Mygind; Astrup, Birgitte Schmidt

    2017-09-01

    Suicide using a combination of a plastic bag over the head and inhalation of a non-irritating gas, such as helium, argon or nitrogen, has been reported in the literature. Here an unusual suicide method in a 17-year old man by suffocation from covering the face with household plastic wrap, combined with nitrous oxide inhalation, is presented. The case was reviewed based on police, autopsy and hospital reports. A PubMed search for scientific literature related to nitrous oxide abuse and suicide by suffocation was performed and our findings discussed in relation to the scientific literature found. The deceased was a 17-year old man who was found with the nose and mouth closed with a piece of kitchen plastic wrap. The plastic wrap had been removed prior to autopsy. Autopsy findings were suggestive of asphyxia, but were otherwise negative. Nitrous oxide was detected in the brain and lung tissue with headspace-gas chromatography-mass spectrometry (headspace-GCMS). The cause of death was assumed to be suffocation caused by plastic wrap covering the face, combined with nitrous oxide inhalation. Suicide was suspected because of a history of depression for several months. Nitrous oxide, also known as laughing gas, has a euphoric effect and is used as a recreational inhalant drug that can be purchased legally. Deaths caused by recreational nitrous oxide abuse are rare but may occur if used in combination with a plastic bag over the head. This is the first report of suicide by suffocation by external obstruction combined with nitrous oxide inhalation.

  5. Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals.

    Science.gov (United States)

    Unfried, Klaus; Krämer, Ursula; Sydlik, Ulrich; Autengruber, Andrea; Bilstein, Andreas; Stolz, Sabine; Marini, Alessandra; Schikowski, Tamara; Keymel, Stefanie; Krutmann, Jean

    2016-01-01

    Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial. The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin(®) inhalation solution) leads to a reduction of neutrophilic cells and interleukin-8 (IL-8) levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution. A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined. While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite) were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence interval 0.45-0.93). Extended analyses considering period effects revealed that the percentage of neutrophils in sputum was significantly lower after ectoine inhalation than in the placebo group (P=0.035) even after the washout phase. The current study is the first human trial in which the effects of inhaled ectoine on neutrophilic lung inflammation were investigated. Besides demonstrating beneficial effects on inflammatory sputum parameters, the study proves the feasibility of

  6. Forensic medical evaluation of deaths resulting from inhalation of cigarette lighter refill fuel in Turkey.

    Science.gov (United States)

    Özdemir, Erdinç; Eş, Hüseyin; Demir, Muhammet; Üzün, İbrahim

    2017-01-01

    Voluntary inhalation/abuse of volatile substances is an important public health problem which especially affects adolescent and young populations worldwide and may be encountered in all socioeconomic and cultural levels. Lighter gas abuse-related death is still an important health problem in Turkey. In this study, 25,265 case files and final reports submitted to the Institute of Forensic Medicine of the First Specialization Board between January 2011 and December 2015 were evaluated retrospectively. In 56 of these cases, lighter gas inhalation (n-butane, propane, isobutane) was recorded as the cause of death. All subjects were male with a mean age of 16.8years. According to eyewitness and crime scene investigation reports, in 48 (85.7%) of the cases, a lighter refill container was found at the scene. It was determined that 21.4% of the cases used a plastic bag to increase the effects of lighter gas and 76.8% inhaled the lighter gas via their mouth and nose. The toxicological analysis of the samples taken while hospitalized showed no lighter refill components (n-butane, propane, isobutane) in 66% of the cases, n-butane in 32.1% of the cases, and n-butane+propane+isobutane in 1.9% of the cases. The importance of lighter gas inhalation-related deaths in Turkey has been increasing. Strict measures against the abuse of these very dangerous substances should be undertaken by the mutual efforts of medical specialists and legislators. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Reporting a sudden death due to accidental gasoline inhalation.

    Science.gov (United States)

    Martínez, María Antonia; Ballesteros, Salomé; Alcaraz, Rafael

    2012-02-10

    The investigation of uncertain fatalities requires accurate determination of the cause of death, with assessment of all factors that may have contributed to it. Gasoline is a complex and highly variable mixture of aliphatic and aromatic hydrocarbons that can lead to cardiac arrhythmias due to sensitization of the myocardium to catecholamines or acts as a simple asphyxiant if the vapors displace sufficient oxygen from the breathing atmosphere. This work describes a sudden occupational fatality involving gasoline. The importance of this petroleum distillate detection and its quantitative toxicological significance is discussed using a validated analytical method. A 51 year-old Caucasian healthy man without significant medical history was supervising the repairs of the telephone lines in a manhole near to a gas station. He died suddenly after inhaling gasoline vapors from an accidental leak. Extensive blistering and peeling of skin were observed on the skin of the face, neck, anterior chest, upper and lower extremities, and back. The internal examination showed a strong odor of gasoline, specially detected in the respiratory tract. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography with flame ionization detector and confirmation was performed using gas chromatography-mass spectrometry. Disposition of gasoline in different tissues was as follows: heart blood, 35.7 mg/L; urine, not detected; vitreous humor, 1.9 mg/L; liver, 194.7 mg/kg; lung, 147.6 mg/kg; and gastric content, 116,6 mg/L (2.7 mg total). Based upon the toxicological data along with the autopsy findings, the cause of death was determined to be gasoline poisoning and the manner of death was accidental. We would like to alert on the importance of testing for gasoline, and in general for volatile hydrocarbons, in work-related sudden deaths involving inhalation of hydrocarbon vapors and/or exhaust fumes. Copyright © 2011 Elsevier Ireland Ltd. All rights

  8. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nolan, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2015-10-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Inhaled dry powder mannitol is now available in Australia and some countries in Europe. The exact mechanism of action of mannitol is unknown, but it increases mucociliary clearance. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 16 April 2015. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The searches identified nine separate studies (45 publications), of which four studies (36 publications) were included with a total of 667 participants, one study (only available as an abstract) is awaiting assessment and two studies are ongoing. Duration of treatment in the included studies ranged from two weeks to six months with open-label treatment for an additional six months in two of the studies. Three studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol); two of these were parallel studies with a similar design and data could be pooled, where data for a particular outcome and time point were available; also, one short

  9. Umidificação e aquecimento do gás inalado durante ventilação artificial com baixo fluxo e fluxo mínimo de gases frescos Humidificación y calentamiento del gas inhalado durante ventilación artificial con bajo flujo y flujo mínimo de gases frescos Inhaled gases humidification and heating during artificial ventilation with low flow and minimal fresh gases flow

    Directory of Open Access Journals (Sweden)

    Susane Bruder Silveira Gorayb

    2004-02-01

    calentamiento del gas inhalado son necesarios para la prevención de lesiones en el sistema respiratorio, consecuentes al contacto del gas frío y seco con las vías aéreas. El objetivo de la pesquisa fue evaluar el efecto del sistema respiratorio circular con absorbedor de dióxido de carbono del aparato de anestesia Cícero de Dräger, cuanto a la capacidad de calentamiento y humidificación de los gases inhalados, utilizándose flujo bajo (1 L.min-1 o mínimo (0,5 L.min-1 de gases frescos. MÉTODO: El estudio aleatorio fue realizado en 24 pacientes estado físico ASA I, con edades entre 18 y 65 años, sometidos a anestesia general, utilizándose la Estación de Trabajo Cícero de Dräger (Alemania, para realización de cirugías abdominales, los cuales fueron distribuidos aleatoriamente en dos grupos: grupo de Bajo Flujo (BF, en el cual fue administrado 0,5 L.min-1 de oxígeno y 0,5 L.min-1 de óxido nitroso y flujo mínimo (FM, administrándose solamente oxígeno a 0,5 L.min-1. Los atributos estudiados fueron: temperatura, humedad relativa y absoluta de la sala de operación y del gas en el sistema inspiratorio. RESULTADOS: Los valores de la temperatura, humedad relativa y humedad absoluta en el sistema inspiratorio en la salida del aparato de anestesia y junto al tubo traqueal no presentaron diferencia significante entre los grupos, pero aumentaron a lo largo del tiempo en los dos grupos (BF y FM, habiendo influencia de la temperatura de la sala de operación sobre la temperatura del gas inhalado, en los dos grupos estudiados. Niveles de humedad y temperatura próximos de los ideales fueron alcanzados, en los dos grupos, a partir de 90 minutos. CONCLUSIONES: No hay diferencia significante de la humedad y temperatura del gas inhalado utilizándose bajo flujo y flujo mínimo de gases frescos.BACKGROUND AND OBJECTIVES: Inhaled gas humidification and heating are necessary in patients under tracheal intubation or tracheostomy to prevent damage to respiratory system resulting

  10. Influence of peak inspiratory flow rates and pressure drops on inhalation performance of dry powder inhalers.

    Science.gov (United States)

    Hira, Daiki; Okuda, Tomoyuki; Ichihashi, Mika; Mizutani, Ayano; Ishizeki, Kazunori; Okada, Toyoko; Okamoto, Hirokazu

    2012-01-01

    The aim of this study was to reveal the relationship between human inspiratory flow patterns and the concomitant drops in pressure in different inhalation devices, and the influence of the devices on inhalation performance. As a model formulation for inhalers, a physically mixed dry powder composed of salbutamol sulfate and coarse lactose monohydrate was selected. The drops in pressure at 28.3 L/min of three inhalation devices, Single-type, Dual-type, and Reverse-type, was 1.0, 5.1, and 8.7 kPa, respectively. Measurements of human inspiratory patterns revealed that although the least resistant device (Single) had large inter- and intra-individual variation of peak flow rate (PFR), the coefficients of variation of PFR of the three devices were almost the same. In tests with a human inspiratory flow simulator in vitro, inhalation performance was higher, but the variation in inhalation performance in the range of human flow patterns was wider, for the more resistant device. To minimize the intra- and inter-individual variation in inhalation performance for the model formulation in this study, a formulation design that allows active pharmaceutical ingredient to detach from the carrier with a lower inhalation flow rate is needed.

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

    NARCIS (Netherlands)

    Grasmeijer, Floris

    2014-01-01

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

  12. Use of inhaled heparin/N-acetylcystine in inhalation injury: does it help?

    Science.gov (United States)

    Holt, Joshua; Saffle, Jeffrey R; Morris, Stephen E; Cochran, Amalia

    2008-01-01

    Inhaled heparin/N-acetylcystine (AHA) has been reported to decrease mortality in children with inhalation injury. The use of AHA therapy in adult burn patients with inhalation injury has not been evaluated. We hypothesized that patients who received AHA therapy in the management of inhalation injury would have better pulmonary mechanics and better clinical outcomes than patients who did not. This study is a retrospective chart review of pulmonary mechanics and clinical outcomes in all inpatients identified in the institutional ABA/TRACS database as having sustained inhalation injury from 1999 to 2005. Patients were not assigned to a treatment group. One hundred and fifty patients with inhalation injury were identified. Sixty-two patients were treated with AHA during the first 72 hours of admission. Treatment occurred mostly in patients admitted after 2002, with only 18 patients receiving AHA from 1999 through 2002. Treated and untreated patients did not differ in age or TBSA burn injury, nor did any studied clinical outcome differ between treated and untreated groups. In addition, there was no difference in pulmonary findings at 1 week after injury between treated and untreated patients. Although best Pao2 was higher in treated patients during the first 72 hours, this was not a durable finding, and the best Pao2/Fio2 ratio was unaffected by treatment. Importantly, the use of AHA in adults with inhalation injury did not affect clinical outcomes. A prospective, randomized trial would be of benefit to delineate the clinical benefits of AHA treatment for inhalation injury.

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

    Directory of Open Access Journals (Sweden)

    Ciciliani A

    2017-05-01

    Full Text Available Anna-Maria Ciciliani,1,2 Peter Langguth,1 Herbert Wachtel2 1Institute of Pharmacy and Biochemistry, Faculty 09 (Chemistry, Pharmaceutics and Geosciences, Johannes Gutenberg University, Mainz, 2Analytical Development Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Background: Combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD treatment.Methods: The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI. Idealized breathing patterns from COPD patient groups – moderate and very severe COPD – were applied. Theoretical lung deposition patterns were assessed by an individual path model.Results and conclusion: For the Respimat the mDTL was found to be 59% (SD 5% for the moderate COPD breathing pattern and 67% (SD 5% for very severe COPD breathing pattern. The percentages refer to nominal dose (ND in vitro. This is in the range of 44%–63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2% for moderate disease simulation and 51% (SD 2% for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2% for moderate and 42% (SD 1% for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3% for moderate and 55% (SD 2% for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3% and 41% (SD 2%, respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that

  14. Genotoxicity of inhaled nanosized TiO(2) in mice.

    Science.gov (United States)

    Lindberg, Hanna K; Falck, Ghita C-M; Catalán, Julia; Koivisto, Antti J; Suhonen, Satu; Järventaus, Hilkka; Rossi, Elina M; Nykäsenoja, Heli; Peltonen, Yrjö; Moreno, Carlos; Alenius, Harri; Tuomi, Timo; Savolainen, Kai M; Norppa, Hannu

    2012-06-14

    In vitro studies have suggested that nanosized titanium dioxide (TiO(2)) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO(2) genotoxicity exist. Recently, nanosized TiO(2) administered in drinking water was reported to increase, e.g., micronuclei (MN) in peripheral blood polychromatic erythrocytes (PCEs) and DNA damage in leukocytes. Induction of micronuclei in mouse PCEs was earlier also described for pigment-grade TiO(2) administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO(2) due to inflammation. However, a recent study suggested that induction of DNA damage in mouse bronchoalveolar lavage (BAL) cells after intratracheal instillation of nanosized or fine TiO(2) is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO(2) (74% anatase, 26% brookite; 5 days, 4 h/day) at 0.8, 7.2, and (the highest concentration allowing stable aerosol production) 28.5 mg/m(3) could induce genotoxic effects in C57BL/6J mice locally in the lungs or systematically in peripheral PCEs. DNA damage was assessed by the comet assay in lung epithelial alveolar type II and Clara cells sampled immediately following the exposure. MN were analyzed by acridine orange staining in blood PCEs collected 48 h after the last exposure. A dose-dependent deposition of Ti in lung tissue was seen. Although the highest exposure level produced a clear increase in neutrophils in BAL fluid, indicating an inflammatory effect, no significant effect on the level of DNA damage in lung epithelial cells or micronuclei in PCEs was observed, suggesting no genotoxic effects by the 5-day inhalation exposure to nanosized TiO(2) anatase. Our inhalation exposure resulted in much lower systemic TiO(2) doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO(2) than

  15. Assessing inhalation injury in the emergency room

    Directory of Open Access Journals (Sweden)

    Tanizaki S

    2015-07-01

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

  16. Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA® Dry Powder Inhaler.

    Science.gov (United States)

    Prime, David; de Backer, Wilfried; Hamilton, Melanie; Cahn, Anthony; Preece, Andrew; Kelleher, Dennis; Baines, Amanda; Moore, Alison; Brealey, Noushin; Moynihan, Jackie

    2015-12-01

    Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA® DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion. For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6-142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p  0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker. All participants achieved a maximal effort PIFR ≥ 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity

  17. Hypercapnia shortens emergence time from inhaled anesthesia in pigs.

    Science.gov (United States)

    Gopalakrishnan, Nishant A; Sakata, Derek J; Orr, Joseph A; McJames, Scott; Westenskow, Dwayne R

    2007-04-01

    Anesthetic clearance from the lungs and the circle rebreathing system can be maximized using hyperventilation and high fresh gas flows. However, the concomitant clearance of CO2 decreases PAco2, thereby decreasing cerebral blood flow and slowing the clearance of anesthetic from the brain. This study shows that in addition to hyperventilation, hypercapnia (CO2 infusion or rebreathing) is a significant factor in decreasing emergence time from inhaled anesthesia. We anesthetized seven pigs with 2 MACPIG of isoflurane and four with 2 MACPIG of sevoflurane. After 2 h, anesthesia was discontinued, and the animals were hyperventilated. The time to movement of multiple limbs was measured under hypocapnic (end-tidal CO2 = 22 mm Hg) and hypercapnic (end-tidal CO2 = 55 mm Hg) conditions. The time between turning off the vaporizer and to movement of multiple limbs was faster with hypercapnia during hyperventilation. Emergence time from isoflurane and sevoflurane anesthesia was shortened by an average of 65% with rebreathing or with the use of a CO2 controller (P hyperventilation, may be used clinically to decrease emergence time from inhaled anesthesia. These time savings might reduce drug costs. In addition, higher PAco2 during emergence may enhance respiratory drive and airway protection after tracheal extubation.

  18. Dry-Powder Inhaler Formulation of Rifampicin: An Improved Targeted Delivery System for Alveolar Tuberculosis.

    Science.gov (United States)

    Rawal, Tejal; Kremer, Laurent; Halloum, Iman; Butani, Shital

    2017-12-01

    The delivery of antitubercular drugs through direct lung targeting can lead to reduction in the dose as well as side effects of the drug. In the present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin was prepared to achieve direct targeting of the drug into the lungs. The dry powder inhaler formulation was prepared by simply mixing micronized rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug were prepared with various lactose grades (Inhalac ® , Respitose, ® and Lactohale ® ). Rotahaler ® and Revolizer ® were evaluated for the performance. The 3 2 factorial design was used to optimize the amount of drug (X 1 ) and amount of fine lactose (X 2 ). In vitro lung deposition was carried out using Andersen Cascade Impactor. The % cell viability studies of the formulation were carried out using murine macrophage J774 cell lines. The in vivo toxicity was determined using histopathology. Further in vivo pulmonary pharmacokinetics of the developed dry-powder inhaler (DPI) formulation was carried out in comparison to the marketed formulation in the rat lungs. Based on preliminary trials, Inhalac 230 and Inhalac 400 were selected as coarse and fine lactose grades, respectively. Rotahaler ® exhibited better DPI performance with the evaluated drug blends. The mass median aerodynamic diameter (MMAD) was in the range of 4.3-5.8 μm with the maximum fine particle fraction of 28.9%. The formulation exhibited negligible cytotoxicity on macrophage J774 cell lines with about 75%-80% cell viability at 6- and 12-hour exposure. The histopathological examination revealed negligible toxicity of DPI in comparison to the marketed formulation. The in vivo pulmonary pharmacokinetic studies of the DPI formulation in rats showed higher drug concentration in lungs in comparison to the marketed formulation. The carrier-mediated dry-powder inhaler of rifampicin could serve as an improved and efficient system for local targeting of drugs

  19. In vivo effects of Aphanizomenon flos-aquae DC-1 aphantoxins on gas exchange and ion equilibrium in the zebrafish gill

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Delu, E-mail: deluzh@163.com [Department of Lifescience and Biotechnology, College of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070 (China); Liu, Siyi [Department of Lifescience and Biotechnology, College of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070 (China); Zhang, Jing [College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Zhang, Jian Kong [Department of Lifescience and Biotechnology, College of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan 430070 (China); Hu, Chunxiang, E-mail: deluzh@ihb.ac.cn [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China); Liu, Yongding [Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072 (China)

    2016-08-15

    Highlights: • Aphantoxins induce respiratory dysfunction in zebrafish gills. • Changes in LDH and cellular ultrastructure indicate gill damage. • Decreased NKA and CA reflect abnormal ion transport and gas exchange. • Increased ROS and decreased T-AOC suggest oxidative stress in the gills. - Abstract: Aphantoxins, neurotoxins or paralytic shellfish poisons (PSPs) generated by Aphanizomenon flos-aquae, are a threat to environmental safety and human health in eutrophic waters worldwide. The molecular mechanisms of neurotoxin function have been studied; however, the effects of these neurotoxins on oxidative stress, ion transport, gas exchange, and branchial ultrastructure in fish gills are not fully understood. Aphantoxins extracted from A. flos-aquae DC-1 were detected by high-performance liquid chromatography. The major ingredients were gonyautoxins 1 and 5 and neosaxitoxin, which comprised 34.04%, 21.28%, and 12.77% of the total, respectively. Zebrafish (Danio rerio) were administered A. flos-aquae DC-1 aphantoxins at 5.3 or 7.61 μg saxitoxin equivalents (eq)/kg (low and high doses, respectively) by intraperitoneal injection. The activities of Na{sup +}-K{sup +}-ATPase (NKA), carbonic anhydrase (CA), and lactate dehydrogenase (LDH), ultrastructural alterations in chloride and epithelial cells, and reactive oxygen species (ROS) and total antioxidative capacity (T-AOC) were investigated in the gills during the first 24 h after exposure. Aphantoxins significantly increased the level of ROS and decreased the T-AOC in zebrafish gills from 3 to 12 h post-exposure, suggesting an induction of oxidative stress and inhibition of antioxidant capacity. Reduced activities of NKA and CA demonstrated abnormal ion transport and gas exchange in the gills of aphantoxin-treated fish. Toxin administration also resulted in increased LDH activity and ultrastructural alterations in chloride and epithelial cells, suggesting a disruption of function and structure in zebrafish

  20. Changes in in vitro gas and methane production from rumen fluid from dairy cows during adaptation to feed additives in vivo.

    Science.gov (United States)

    Klop, G; van Laar-van Schuppen, S; Pellikaan, W F; Hendriks, W H; Bannink, A; Dijkstra, J

    2017-04-01

    The adaptation of dairy cows to methane (CH4)-mitigating feed additives was evaluated using the in vitro gas production (GP) technique. Nine rumen-fistulated lactating Holstein cows were grouped into three blocks and within blocks randomly assigned to one of three experimental diets: Control (CON; no feed additive), Agolin Ruminant® (AR; 0.05 g/kg dry matter (DM)) or lauric acid (LA; 30 g/kg DM). Total mixed rations composed of maize silage, grass silage and concentrate were fed in a 40 : 30 : 30 ratio on DM basis. Rumen fluid was collected from each cow at days -4, 1, 4, 8, 15 and 22 relative to the introduction of the additives in the diets. On each of these days, a 48-h GP experiment was performed in which rumen fluid from each individual donor cow was incubated with each of the three substrates that reflected the treatment diets offered to the cows. DM intake was on average 19.8, 20.1 and 16.2 kg/day with an average fat- and protein-corrected milk production of 30.7, 31.7 and 26.2 kg/day with diet CON, AR and LA, respectively. In general, feed additives in the donor cow diet had a larger effect on gas and CH4 production than the same additives in the incubation substrate. Incubation substrate affected asymptotic GP, half-time of asymptotic CH4 production, total volatile fatty acid (VFA) concentration, molar proportions of propionate and butyrate and degradation of organic matter (OMD), but did not affect CH4 production. No substrate×day interactions were observed. A significant diet×day interaction was observed for in vitro gas and CH4 production, total VFA concentration, molar proportions of VFA and OMD. From day 4 onwards, the LA diet persistently reduced gas and CH4 production, total VFA concentration, acetate molar proportion and OMD, and increased propionate molar proportion. In vitro CH4 production was reduced by the AR diet on day 8, but not on days 15 and 22. In line with these findings, the molar proportion of propionate in fermentation fluid was

  1. Effect of terbutaline on mucociliary clearance in asthmatic and healthy subjects after inhalation from a pressurised inhaler and a dry powder inhaler.

    Science.gov (United States)

    Mortensen, J; Groth, S; Lange, P; Hermansen, F

    1991-01-01

    BACKGROUND: beta Agonists have been shown to increase mucociliary clearance in some studies but not all. Whether the formulation of beta agonists affects mucociliary clearance is not known but may be important as the use of dry powder inhalers increases. METHODS: The effect of different methods of administration of inhaled terbutaline on mucociliary clearance and forced expiratory volume in one second (FEV1) was assessed in 10 patients with asthma and 10 healthy subjects. Terbutaline (1 mg) was administered through a metered dose inhaler with a spacer (Nebuhaler) or a dry powder inhaler (Turbuhaler), or both treatments were given, in a four way double blind, double dummy trial. Mucociliary clearance was measured by bronchoscintigraphy. RESULTS: Clearance of radioactivity from the lobar bronchi increased in the asthmatic patients by a median of 32% after terbutaline was given by metered dose inhaler and 55% after a combined dose of 2 mg from both inhalers (1 mg from each) compared with placebo but by only 9% after 1 mg of terbutaline was given by a dry powder inhaler. In the healthy subjects mucociliary clearance increased by 51% when terbutaline was given by a dry powder inhaler, by 66% when given by a metered dose inhaler, and by 66% when given by both inhalers combined. The effect of terbutaline on FEV1 was the same with each of the inhalers. CONCLUSION: Despite similar changes in FEV1 with the two formulations terbutaline increased mucociliary clearance significantly in asthmatic and healthy subjects when inhaled from a metered dose inhaler whereas when it was inhaled from a dry powder inhaler its effect was significant only in healthy subjects. The reason for the difference in asthmatic subjects is unclear, but may be associated with differences in the deposition of terbutaline. Images PMID:1771605

  2. Deposition and biokinetics of inhaled nanoparticles

    Science.gov (United States)

    2010-01-01

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

  3. The sites of respiratory gas exchange in the planktonic crustacean daphnia magna: an in vivo study employing blood haemoglobin as an internal oxygen probe

    Science.gov (United States)

    Pirow; Wollinger; Paul

    1999-11-01

    Recent studies on Daphnia magna have revealed that the feeding current is important for uptake of oxygen from the ambient medium. Respiratory gas exchange should therefore mainly occur within the filtering chamber, whose boundaries are formed by the trunk and the extended carapace shell valves. The precise site of gas exchange in the genus Daphnia is, however, a matter of conjecture. We have developed a method of imaging the haemoglobin oxygen-saturation in the circulatory system of transparent animals, which provides an opportunity to localize oxygen uptake from the environment and oxygen release to the tissues. Experiments were carried out at 20 degrees C on 2.8-3.0 mm long parthenogenetic females maintained in hypoxic culturing conditions, which had resulted in an increased haemoglobin content in the haemolymph. In lateral views of D. magna, the highest values of haemoglobin oxygen-saturation occurred near the posterior margin of the carapace and, surprisingly, in the rostral part of the head. The ambient oxygen partial pressures at which haemoglobin was half-oxygenated were 15 mmHg (2.0 kPa) for the posterior carapace region and 6 mmHg (0.8 kPa) for the rostrum. Although not all parts of the circulatory system could be analyzed using this technique, the data obtained from the accessible regions suggest that the inner wall of the carapace is a major site of respiratory gas exchange. Taking the circulatory pattern and the flow pattern of the medium in the filtering chamber into consideration, it becomes clear that the haemolymph, after passing from the limbs to the carapace lacuna, becomes oxygenated while flowing through the ventral part of the double-walled carapace in a posterior direction. The laterally flattened rostral region, where sensory and central nervous system structures are located, seems to have direct diffusive access to ambient oxygen, which could be especially advantageous during severe hypoxia when the convective transport systems fail to

  4. Characterisation and functionality of inhalation anhydrous lactose.

    Science.gov (United States)

    Pitchayajittipong, Chonladda; Price, Robert; Shur, Jagdeep; Kaerger, J Sebastian; Edge, Stephen

    2010-05-10

    The relationships between the physicochemical properties and functionality in dry powder inhaler (DPI) performance was investigated for inhalation grade anhydrous lactose and compared to monohydrate grades. The excipients were characterised using a range of techniques including particle size analysis, moisture sorption and powder rheometry. The inhalation anhydrous lactose grades were readily characterisable. The aerosolisation performance of capsule based DPI formulations containing budesonide (200microg) and different grades of lactose evaluated using inertial impaction measurements produced fine particle doses of budesonide ranging from 24 to 49microg. There were no apparent relationships between aerosolisation performance and excipient characteristics, such as particle size and powder density. However, formulations containing lactose grades which exhibit higher powder fluidisation energy values resulted in higher fine particle doses of budesonide. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Inhaled hyaluronic acid microparticles extended pulmonary retention and suppressed systemic exposure of a short-acting bronchodilator

    DEFF Research Database (Denmark)

    Li, Ying; Han, Meihua; Liu, Tingting

    2017-01-01

    into inhalable microparticles, which were subsequently characterized as spherical shape with wrinkled surface. The fine particle fraction of the microparticles tested by using the Next Generation Impactor was over 30% without the aid of any carrier, and the in vitro release of SAS lasted for 20h. Compared...... to spray-dried plain SAS powders, the SAS-loaded HA microparticles possessed enhanced biomucoadhesive property in vitro and had much longer pulmonary retention and reduced systemic exposure in vivo. By incorporation, the pulmonary retention time of SAS was prolonged from 2h to 8h while the maximum...... concentration in plasma was reduced significantly from 2267.7ng/mL to 566.38ng/mL. These results suggested that inhaled HA microparticles could be a promising formulation strategy to enhance the therapeutic efficacy of inhaled medicines....

  6. Social stigma stops adolescents from using inhalers for asthma.

    Science.gov (United States)

    2017-07-10

    Forgetfulness, poor routines, inadequate inhaler technique, organisational difficulties and families not understanding or accepting their children's asthma are described as barriers to the use of inhalers among adolescents with asthma.

  7. Cow Dung Ingestion and Inhalation Dependence: A Case Report

    Science.gov (United States)

    Khairkar, Praveen; Tiple, Prashant; Bang, Govind

    2009-01-01

    Although abuse of several unusual inhalants had been documented, addiction to cow dung fumes or their ashes has not been reported in medical literature as yet. We are reporting a case of cow dung dependence in ingestion and inhalational form.

  8. [Easyhaler--ideal dry powder inhaler].

    Science.gov (United States)

    Andrzej, Emeryk; Małgorzata, Bartkowiak-Emeryk

    2010-04-01

    Dry powder inhalers (DPI) differ among each other in many technical aspects, size and value of lung deposition as well as clinical efficacy of inhaled drugs. Easyhaler is a reservoir, multi-dose, high-resistance DPI and it is easy to operate. The device needs low inspiratory flows which are possible to achieve even by asthmatic children over 5-year-old and emitted dose and fine particle fraction are practically stable within the range of optimal inspiratory flows. Currently budesonid, formoterol and salbutamol are available in Easyhaler device form. Easyhaler is accepted by majority of patients with asthma or COPD.

  9. Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.

    Science.gov (United States)

    Brocklebank, D; Ram, F; Wright, J; Barry, P; Cates, C; Davies, L; Douglas, G; Muers, M; Smith, D; White, J

    2001-01-01

    for further information. Trials that met the inclusion criteria were appraised and data extraction was under-taken by one reviewer and checked by a second reviewer, with any discrepancies being resolved through agreement. RESULTS--IN VITRO CHARACTERISTICS VERSUS IN VIVO TESTING AND CLINICAL RESPONSE: There is evidence that when comparative testing is performed on inhaler devices using the same methods, there is some correlation between particle size measurements and clinical response. However, the measurements are dependent upon the methods used, and a single measure of a device in isolation is of limited value. Also, there is little data on comparing devices of different types. There is currently insufficient data to verify the ability of in vitro assessments to predict inhaler performance in vivo. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF CORTICOSTEROIDS IN ASTHMA: The review of three trials in children and 21 trials in adults demonstrated no evidence to suggest clinical benefits of any other inhaler device over a pMDI in corticosteroid delivery. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN STABLE ASTHMA: In children, 11 studies were reviewed, of which seven compared the Turbohaler with the pMDI. One study found a significant treatment difference in peak expiratory flow rate, although there were differences in the patients' baseline characteristics. In adults, a review of 70 studies found no demonstrable difference in the clinical bronchodilator effect of short-acting b2-agonists delivered by the standard pMDI compared with that produced by any other DPI, HFA-pMDI or the Autohaler device. The finding that HFA-pMDIs may reduce treatment failure and oral steroid requirement in beta-agonist delivery needs further confirmatory research in adequately randomised clinical trials. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN STABLE ASTHMA: In

  10. Compared biokinetic and biological studies of chronic and acute inhalations of uranium compounds in the rat; Etudes biocinetique et biologique comparees d'inhalations chroniques et aigues de composes uraniferes chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Monleau, M

    2005-12-15

    Uranium is a natural, radioactive heavy metal, widely used in the nuclear industry in various chemical and isotopic forms. Its use in the fuel cycle involves the risk of radiological exposure for the workers, mainly via the inhalation of uranium particles. According to the workplace configuration, uranium contaminations can be acute or repeated, involve various chemical forms and different levels of enrichment, as well as involving one or several components. The dosimetric concepts and models available for workers' radiological protection, as well as most of the studies of the biological effects, correspond to acute exposure situations. Moreover the processes leading to pathological effects are little known in vivo. In this context, the main question is to know whether exposures due to repeated inhalation by rats induce the element kinetics and toxicity, which may be different from those observed after an acute exposure. In this study, comparison of the experimental and theoretical biokinetics of an insoluble uranium repeatedly inhaled over three weeks shows that a chronic contamination is correctly modelled, except for bone retention, by the sum of acute, successive and independent incorporations. Moreover, the kinetics of a soluble uranium inhaled irregularly can be modified by previous repeated exposure to an insoluble uranium. In certain cases therefore, exposure to uranium could modify its biokinetics during later exposures. At a toxicological level, the study demonstrates that the uranium particles inhaled repeatedly induce behavioural disruptions and genotoxic effects resulting in various sorts of DNA damage, in several cell types and certainly depending on the quantity inhaled. Exposures involving several uraniferous components produce a synergy effect. Moreover, repeated inhalations worsen the genotoxic effects in comparison to an acute exposure. This work demonstrates the importance of not ignoring the effects of the repetition of uranium exposure

  11. SEVOFLURANE, DESFLURANE, AND XENON NEW INHALED ANESTHETICS IN VETERINARY MEDICINE

    OpenAIRE

    Cláudio Correa Natalini

    2001-01-01

    Inhalation anesthesia is widely used in veterinary medicine. New inhalation anesthetics that present less untoward effects, are more potent and produce a safe and easily changeable anesthetic plane are desirable over the older agents presently available. In this review some of the physical and chemical aspects of inhalation anesthesia is revisited. Because the agents used in inhalation anesthesia are gases or vapors, the physics of vaporization, delivery and administration of these agents sho...

  12. NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

    Science.gov (United States)

    Coote, K J; Paisley, D; Czarnecki, S; Tweed, M; Watson, H; Young, A; Sugar, R; Vyas, M; Smith, N J; Baettig, U; Groot-Kormelink, P J; Gosling, M; Lock, R; Ethell, B; Williams, G; Schumacher, A; Harris, J; Abraham, W M; Sabater, J; Poll, C T; Faller, T; Collingwood, S P; Danahay, H

    2015-06-01

    Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds. © 2015 The British Pharmacological Society.

  13. Can patients use all dry powder inhalers equally well?

    NARCIS (Netherlands)

    Gustafsson, P; Taylor, A; Zanen, P; Chrystyn, H

    2005-01-01

    If patients are unable to use their inhaler, drug delivery may be unsatisfactory and the patients may fail to benefit from the prescribed medication. It is important to consider whether patients can use all dry powder inhalers equally well. Changing a patient from a dry powder inhaler used well to

  14. Laser-polarized xenon-129 magnetic resonance spectroscopy and imaging. The development of a method for in vivo perfusion measurement

    Science.gov (United States)

    Rosen, Matthew Scot

    2001-07-01

    This thesis presents in vivo nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) studies with laser-polarized 129Xe delivered to living rats by inhalation and transported to tissue via blood flow. The results presented herein include the observation, assignment, and dynamic measurement of 129Xe resonances in the brain and body, the first one- and two-dimensional chemical-shift-resolved images of 129Xe in blood, tissue, and gas in the thorax, and the first images of 129Xe in brain tissue. These results establish that laser-polarized 129Xe can be used as a magnetic resonance tracer in vivo. NMR resonances at 0, 191, 198, and 209 ppm relative to the 129 Xe gas resonance are observed in the rat thorax and assigned to 129Xe in gas, fat, tissue, and blood respectively. Resonances at 189, 192, 195, 198, and 209 ppm are observed in the brain, and the 195 and 209 ppm resonances are assigned to 129Xe in grey matter, and blood, respectively. The design and construction of a laser-polarized 129Xe production and delivery system is described. This system produces liter-volumes of laser- polarized 129Xe by spin-exchange optical- pumping. It represented an order of magnitude increase over previously reported production volumes of polarized 129Xe. At approximately 3-7% polarization, 157 cc-atm of xenon is produced and stored as ice every 5 minutes. This reliable, effective, and simple production method for large volumes of 129Xe can be applied to other areas of research involving the use of laser-polarized noble gases. A model of the in vivo transport of laser polarized 129Xe to tissue under realistic experimental NMR conditions is described. Appropriate control of the NMR parameters is shown to allow tissue perfasion and 129Xe tissue T1 to be extracted from measurement of the steady-state 129Xe tissue signal. In vivo rodent 129Xe NMR results are used to estimate the signal-to-noise ratio of this technique, and an inhaled 30% xenon/70% O2 mixture polarized to 5

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-01

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

  16. Cigarette smoke enhances Th-2 driven airway inflammation and delays inhalational tolerance

    Directory of Open Access Journals (Sweden)

    Joos Guy F

    2008-05-01

    Full Text Available Abstract Background Active smoking increases asthma severity and is related to diminished treatment efficacy. Animal models in which inhalation of both allergen and mainstream cigarette smoke are combined can help us to understand the complex interaction between both agents. We have recently shown that, in allergic mice, the airway inflammation can be cleared by repeated allergen challenge, resulting in the establishment of a state of inhalational tolerance. Methods In this study, we assessed in vivo the impact of cigarette smoke on the efficacy and time course of this form of tolerance induction. We exposed sensitized mice to concurrent mainstream cigarette smoke and allergen (Ovalbumin- OVA and measured the airway inflammation at different time points. Results We first confirmed that aerosolized OVA administered for a prolonged time period (4–8 weeks resulted in the establishment of tolerance. Concurrent OVA and smoke exposure for 2 weeks showed that tobacco smoke enhanced the Th-2 driven airway inflammation in the acute phase. In addition, the induction of the tolerance by repeated inhalational OVA challenge was delayed significantly by the tobacco smoke, since 4 weeks of concurrent exposure resulted in a more persistent eosinophilic airway inflammation, paralleled by a more mature dendritic cell phenotype. However, smoke exposure could not prevent the establishment of tolerance after 8 weeks of antigen exposure as shown by both histopathology (disappearance of the Th-2 driven inflammation and by in vivo functional experiments. In these tolerized mice, some of the inflammatory responses to the smoke were even attenuated. Conclusion Cigarette smoke enhances acute allergic inflammation and delays, but does not abrogate the development of tolerance due to prolonged challenge with inhaled antigen in experimental asthma.

  17. Inhalation drug delivery devices: technology update

    Directory of Open Access Journals (Sweden)

    Ibrahim M

    2015-02-01

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

  18. [The place of inhaled corticosteroids in COPD].

    Science.gov (United States)

    Chinet, T; Dumoulin, J; Honore, I; Braun, J-M; Couderc, L-J; Febvre, M; Mangiapan, G; Maurer, C; Serrier, P; Soyez, F; Terrioux, P; Jebrak, G

    2016-12-01

    Clinical trials have provided some evidence of a favorable effect of inhaled corticosteroids on the frequency of exacerbations and on the quality of life of patients with chronic obstructive pulmonary disease (COPD). In contrast, ICS have little or no impact on lung function decline and on mortality. Inhaled corticosteroids are recommended only in a minority of COPD patients, those with severe disease and repeated exacerbations and probably those with the COPD and asthma overlap syndrome. However, surveys indicate that these drugs are inappropriately prescribed in a large population of patients with COPD. Overtreatment with inhaled corticosteroids exposes these patients to an increased risk of potentially severe side-effects such as pneumonia, osteoporosis, and oropharyngeal candidiasis. Moreover, it represents a major waste of health-care spending. Primary care physicians as well as pulmonologists should be better aware of the benefits as well as the side-effects and costs of inhaled corticosteroids. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Aerosol Therapy: Nebulizer vs Metered Dose Inhaler

    National Research Council Canada - National Science Library

    Newhouse, M; Dolovich, M

    1987-01-01

    ... aerosol generation using metered-dose inhalers. Previously, aerosol delivery by means of intermittent positive pressure breathing devices attached to nebulizers enjoyed unwarranted popularity for decades, only to be abandoned when convincing evidence became available that they were no better than nebulizers alone for administering bronchodilato...

  20. Manganese Inhalation as a Parkinson Disease Model

    Directory of Open Access Journals (Sweden)

    José Luis Ordoñez-Librado

    2011-01-01

    Full Text Available The present study examines the effects of divalent and trivalent Manganese (Mn2+/Mn3+ mixture inhalation on mice to obtain a novel animal model of Parkinson disease (PD inducing bilateral and progressive dopaminergic cell death, correlate those alterations with motor disturbances, and determine whether L-DOPA treatment improves the behavior, to ensure that the alterations are of dopaminergic origin. CD-1 male mice inhaled a mixture of Manganese chloride and Manganese acetate, one hour twice a week for five months. Before Mn exposure, animals were trained to perform motor function tests and were evaluated each week after the exposure. By the end of Mn exposure, 10 mice were orally treated with 7.5 mg/kg L-DOPA. After 5 months of Mn mixture inhalation, striatal dopamine content decreased 71%, the SNc showed important reduction in the number of TH-immunopositive neurons, mice developed akinesia, postural instability, and action tremor; these motor alterations were reverted with L-DOPA treatment. Our data provide evidence that Mn2+/Mn3+ mixture inhalation produces similar morphological, neurochemical, and behavioral alterations to those observed in PD providing a useful experimental model for the study of this neurodegenerative disease.

  1. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

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

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

  2. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet ... boca) [PDF - 276 KB] Follow @CDCasthma on Twitter to learn more about helping people with asthma live healthier lives by gaining ... Formats Help: How do I view different file formats (PDF, DOC, ...

  3. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov . Asthma Learn How to Control Asthma Brochures Facts Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  4. Systematic Review of Errors in Inhaler Use

    DEFF Research Database (Denmark)

    Sanchis, Joaquin; Gich, Ignasi; Pedersen, Søren

    2016-01-01

    A systematic search for articles reporting direct observation of inhaler technique by trained personnel covered the period from 1975 to 2014. Outcomes were the nature and frequencies of the three most common errors; the percentage of patients demonstrating correct, acceptable, or poor technique; and variations...

  5. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... PDF – 1.1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine exactly as your doctor or other medical professional ...

  6. Elemental Concentration of Inhalable and Respirable Particulate ...

    African Journals Online (AJOL)

    20537 and respirable foam for I.O.M sampler. The elemental composition (Co, Ni, Zn, Cu, Fe, Pb, Cr, Mn and Cd) were analyzed by using Atomic Absorption Spectrophotometric (AAS). The data generated were subjected to descriptive analysis. In inhalable fraction,the enrichment factor ranged from 1-73.3 while in respirable ...

  7. Management of acute smoke inhalation injury.

    Science.gov (United States)

    Toon, Michael H; Maybauer, Marc O; Greenwood, John E; Maybauer, Dirk M; Fraser, John F

    2010-03-01

    Pulmonary injury from smoke inhalation is common in burn victims, significantly contributing to the morbidity and mortality of fire-related injuries. The impacts of improvement in other aspects of burn care have not been mirrored in treatment of smoke inhalation. Smoke is heterogeneous and unique to each fire; it comprises particulates, respiratory irritants and systemic toxins as well as heat, all contributing to the pathological insult. Thermal injury below the vocal cords is rare because of effective heat dissipation in the upper airway. Particulate matter is the chief contributor to the pathophysiology of smoke inhalation injury, which has been extensively described. Of paramount importance is the cascade of inflammatory mediators following interaction of irritant substances with lung parenchyma, leading to pulmonary oedema, cast formation, airway obstruction, loss of hypoxic pulmonary vasoconstriction and ventilation/perfusion mismatch. Current treatment is based on supportive care, with airway management, mechanical ventilation, humidification and aggressive airway toilet the mainstays. Nebulisation of n2-agonists, heparin and N-acetylcysteine have a role in management, as does more specific treatment of carbon monoxide or cyanide intoxication. Many promising treatments are currently under investigation. The therapeutic strategy of decontaminating the lungs early after smoke exposure to prevent inhalation injury has received little attention and may be of significant value. This could potentially utilise amphoteric, hypertonic chelating agents developed for topical and ocular chemical exposures.

  8. Pneumonitis after Inhalation of Mercury Vapours

    Directory of Open Access Journals (Sweden)

    JD Glezos

    2006-01-01

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

  9. Ozone inhalation modifies the rat liver proteome☆

    Science.gov (United States)

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

    2013-01-01

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

  10. Ozone inhalation modifies the rat liver proteome.

    Science.gov (United States)

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

    2014-01-01

    Ozone (O3) is a serious public health concern. Recent findings indicate that the damaging health effects of O3 extend to multiple systemic organ systems. Herein, we hypothesize that O3 inhalation will cause downstream alterations to the liver. To test this, male Sprague-Dawley rats were exposed to 0.5ppm O3 for 8h/day for 5 days. Plasma liver enzyme measurements showed that 5 day O3 exposure did not cause liver cell death. Proteomic and mass spectrometry analysis identified 10 proteins in the liver that were significantly altered in abundance following short-term O3 exposure and these included several stress responsive proteins. Glucose-regulated protein 78 and protein disulfide isomerase increased, whereas glutathione S-transferase M1 was significantly decreased by O3 inhalation. In contrast, no significant changes were detected for the stress response protein heme oxygenase-1 or cytochrome P450 2E1 and 2B in liver of O3 exposed rats compared to controls. In summary, these results show that an environmentally-relevant exposure to inhaled O3 can alter the expression of select proteins in the liver. We propose that O3 inhalation may represent an important unrecognized factor that can modulate hepatic metabolic functions. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Ozone inhalation modifies the rat liver proteome

    Directory of Open Access Journals (Sweden)

    Whitney S. Theis

    2014-01-01

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

  12. Use of inhaled corticosteroids in pediatric asthma

    DEFF Research Database (Denmark)

    Bisgaard, H

    1997-01-01

    to suggest that asthma acts via a chronic inflammatory process that causes remodeling of the airways with mucosal thickening and smooth muscle hypertrophy. An optimal treatment strategy would be one aimed at reducing the ongoing airway inflammation. Inhaled steroids ameliorate the inflammation, whereas...

  13. A breath actuated dry powder inhaler

    NARCIS (Netherlands)

    de Boer, Anne; Frijlink, Henderik W.; Hagedoorn, Paul

    2015-01-01

    A breath actuated dry powder inhaler with a single air circulation chamber for de-agglomeration of entrained powdered medicament using the energy of the inspiratory air stream. The chamber has a substantially polygonal sidewall, a plurality of air supply channels entering the chamber substantially

  14. Know How to Use Your Asthma Inhaler

    Medline Plus

    Full Text Available ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health Know How to Use Your Asthma Inhaler Recommend ... 1 MB] ASL Asthma Film Asthma Clinical Guidelines Air Pollution & Respiratory Health File Formats Help: How do I view different ...

  15. Computational modelling for dry-powder inhalers

    NARCIS (Netherlands)

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

    2012-01-01

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

  16. The dispersion behaviour of dry powder inhalation formulations cannot be assessed at a single inhalation flow rate

    NARCIS (Netherlands)

    Grasmeijer, Floris; de Boer, Anne H.

    2014-01-01

    The dispersion performances of inhalation powders are often tested at only one inhalation flow rate in mechanistic formulation studies. This limited approach is challenged by studies showing that interactions exist between inhalation flow rate and the effects on dispersion performance of several

  17. Effect of inhaled medication and inhalation technique on dental caries in asthmatic patients.

    Science.gov (United States)

    Boskabady, Marzie; Nematollahi, Hossein; Boskabady, Mohammad Hossein

    2012-12-01

    The purpose of this study was to examine the relationship between the type of inhaled medication, length of use, dosing, the inhaler use technique and the severity and duration of disease on the dental caries of asthmatic patients. In the present study, the frequency of dental caries in the asthmatic patients and control group was examined. In addition the possible association of dental caries with disease duration, disease severity, asthma symptoms, chest wheeze, PFT values, and dose of medication and inhalation use technique was evaluated. 40 asthmatic patients of both sex (20-30 years old) and 40 age and sex matched controls were studied. In asthmatic patients, the type, dose, duration of medications, the technique of inhaler use and severity and duration of the disease were recorded. The dental health status including DT, MT, FT and DMFT (decay, missing, filling teeth) were examined. In addition, pulmonary function tests (PFTs) were performed for both groups. All PFT variables in asthmatic patients were significantly lower than those of control group except for FVC (P dental caries in asthmatic group were higher than those of controls which was statistically significant for MT and DMFT (P asthma duration were significantly more than those of 6-10 years (P dental caries and disease duration, PFT values; doses of medication or the technique of inhaler use; although the technique of inhaler use was relatively acceptable in all asthmatic patients. These results showed that dental caries among asthmatic patients was more common than control group which can be due to using inhaler drugs or the technique of inhaler use.

  18. Pharmacokinetics and pharmacodynamics of moist inhalation epinephrine using a mobile inhaler.

    Science.gov (United States)

    Breuer, C; Wachall, B; Gerbeth, K; Abdel-Tawab, M; Fuhr, U

    2013-06-01

    Intramuscular (L-)epinephrine is used as self-medication for serious hypersensitivity reactions. Inhalative administration has the theoretical advantage of a more rapid absorption and better controllability. The current trial was conducted to explore pharmacokinetics and pharmacodynamics of two nebulized inhalative epinephrine doses (4 mg and 8 mg in aqueous solution) using a mobile pocket inhaler relative to intramuscular administration (0.3 mg) and placebo. This randomized, open-label, change-over pilot study involved eight young healthy men and women. Noncompartmental pharmacokinetic and pharmacodynamic parameters were calculated from epinephrine plasma concentrations and hemodynamic parameters. Mean exposure to epinephrine decreased from the 8 mg dose to the 4 mg inhalative dose, and further with the 0.3 mg intramuscular dose, with active treatments showing significantly higher concentrations than placebo (geometric mean area under the curve AUC0-t(last) values: 282, 236, 204 and 81.6 hr*ng/L). Maximal concentrations were reached within approximately 15 min for all active treatments. Epinephrine effects for inhalative administrations on heart rates were significantly higher than those for the intramuscular or placebo administration, while no excessive effects occurred. Pronounced overall variability prohibited a definite assessment of relative bioavailability between treatments. However, results indicated that epinephrine concentrations obtained following the 8 mg inhalative dose were not inferior to those after 0.3 mg i.m. A relevant fraction of moist inhalation epinephrine doses is absorbed and mediates systemic effects. This suggests that administration of epinephrine via a suitable pocket inhaler device may be beneficial in ambulatory emergency treatment of systemic hypersensitivity reactions. EudraCT number: 2010-021493-11.

  19. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-11-01

    Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

  20. Isocapnic hyperventilation shortens washout time for sevoflurane - an experimental in vivo study.

    Science.gov (United States)

    Hallén, K; Stenqvist, O; Ricksten, S-E; Lindgren, S

    2016-10-01

    Isocapnic hyperventilation (IHV) is a method that fastens weaning from inhalation anaesthesia by increasing airway concentration of carbon dioxide (CO2 ) during hyperventilation (HV). In an animal model, we evaluated a technique of adding CO2 directly to the breathing circuit of a standard anaesthesia apparatus. Eight anaesthetised pigs weighing 28 ± 2 kg were intubated and mechanically ventilated. From a baseline ventilation of 5 l/min, HV was achieved by doubling minute volume and fresh gas flow. Respiratory rate was increased from 15 to 22/min. The CO2 absorber was disconnected and CO2 was delivered (DCO2 ) to the inspiratory limb of a standard breathing circuit via a mixing box. Time required to decrease end-tidal sevoflurane concentration from 2.7% to 0.2% was defined as washout time. Respiration and haemodynamics were monitored by blood gas analysis, spirometry, electric impedance tomography and pulse contour analysis. A DCO2 of 261 ± 19 ml/min was necessary to achieve isocapnia during HV. The corresponding FICO2 -level remained stable at 3.1 ± 0.3%. During IHV, washout of sevoflurane was three times faster, 433 ± 135 s vs. 1387 ± 204 s (P CO2 tension and end-tidal CO2 , was 5.2 ± 0.4 kPa and 5.6 ± 0.4%, respectively, before IHV and 5.1 ± 0.3 kPa and 5.7 ± 0.3%, respectively, during IHV. In this experimental in vivo model of isocapnic hyperventilation, the washout time of sevoflurane anaesthesia was one-third compared to normal ventilation. The method for isocapnic hyperventilation described can potentially be transferred to a clinical setting with the intention to decrease emergence time from inhalation anaesthesia. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Inhalational use of antithrombotics in humans: Review of the literature.

    Science.gov (United States)

    Monagle, K; Ryan, A; Hepponstall, M; Mertyn, E; Monagle, P; Ignjatovic, V; Newall, F

    2015-12-01

    Off label use of anticoagulants is common. The association between fibrin deposition in the lungs and primary lung disease, injury or prematurity affords a strong theoretical basis for the potential benefit of antithrombotic therapies administered directly to the lung tissue. This review offers a critical appraisal of current evidence related to the inhalational administration of antithrombotic therapy in humans. An interrogation of 2 databases across a 13 year period of time was undertaken using key words selected a priori. Identified publications were categorized according to the following themes: 1. Inhaled antithrombotic therapy in healthy subjects 2. Inhaled antithrombotic therapy for vascular thromboprophylaxis 3. Inhaled antithrombotic therapy in smoke inhalation and lung injury 4. Inhaled antithrombotic therapy in asthma or allergy 5. Inhaled antithrombotic therapy for plastic bronchitis post-Fontan surgery 6. Inhaled antithrombotic therapy for other indications. 33 articles were identified consistent with the inclusion criteria developed for this review. Unfractionated heparin, LMWH, activated protein C and thrombolytic agents have been administered via the respiratory track, with asthma and smoke inhalation/lung injury being the most frequently investigated clinical scenarios described. All studies reported had significant methodological limitations. The safety and clinical utility of inhaled antithrombotic therapies have not been adequately investigated to support the generation of any firm evidence. This review highlights where inhaled antithrombotic therapies have shown promise and importantly, the further research required to confirm mechanism of action and a definitive risk: benefit profile. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  2. Ex vivo

    Science.gov (United States)

    Matsuda, Kant M; Lopes-Calcas, Ana; Honke, Michael L; O'Brien-Moran, Zoe; Buist, Richard; West, Michael; Martin, Melanie

    2017-07-01

    To advance magnetic resonance imaging (MRI) technologies further for in vivo tissue characterization with histopathologic validation, we investigated the feasibility of ex vivo tissue imaging of a surgically removed human brain tumor as a comprehensive approach for radiology-pathology correlation in histoanatomically identical fashion in a rare case of pigmented ganglioglioma with complex paramagnetic properties. Pieces of surgically removed ganglioglioma, containing melanin and hemosiderin pigments, were imaged with a small bore 7-T MRI scanner to obtain T1-, T2-, and T2*-weighted image and diffusion tensor imaging (DTI). Corresponding histopathological slides were prepared for routine hematoxylin and eosin stain and special stains for melanin and iron/hemosiderin to correlate with MRI signal characteristics. Furthermore, mean diffusivity (MD) maps were generated from DTI data and correlated with cellularity using image analysis. While the presence of melanin was difficult to interpret in in vivo MRI with certainty due to concomitant hemosiderin pigments and calcium depositions, ex vivo tissue imaging clearly demonstrated pieces of tissue exhibiting the characteristic MR signal pattern for melanin with pathologic confirmation in a histoanatomically identical location. There was also concordant correlation between MD and cellularity. Although it is still in an initial phase of development, ex vivo tissue imaging is a promising approach, which offers radiology-pathology correlation in a straightforward and comprehensive manner.

  3. Inhaled nitric oxide improves lung allograft function after prolonged storage.

    Science.gov (United States)

    Okabayashi, K; Triantafillou, A N; Yamashita, M; Aoe, M; DeMeester, S R; Cooper, J D; Patterson, G A

    1996-08-01

    Morbidity caused by early allograft dysfunction, manifested by a progressive increase in pulmonary vascular resistance and a decrease in oxygenation, remains a serious problem in lung transplantation. Inhalation of nitric oxide, an essential homeostatic molecule, has been shown to have beneficial effects on a variety of acute lung injuries. The purpose of the present study was to investigate the effect of inhaled nitric oxide on posttransplant function of canine left lung allografts. Fourteen dogs underwent left lung allotransplantation. Donors received systemic heparin and prostaglandin E1 followed by pulmonary artery flush with modified Euro-Collins solution. Donor left lungs were stored for 18 hours at 1 degree C and subsequently implanted. Immediately after reperfusion, the contralateral right main pulmonary artery and bronchus were ligated. The chest was closed and recipients turned to the supine position for the 6-hour assessment period. Hemodynamic and arterial and venous blood gas analyses were made at 15-minute intervals at an inspired oxygen fraction of 1.0 and 5 cm of water positive end-expiratory pressure. Animals were killed at the end of the assessment. Allograft myeloperoxidase activity assays and wet/dry weight ratios were done. In group I (n = 5), nitric oxide gas was administered continuously at concentrations of 60 to 70 ppm before reperfusion and throughout the 6-hour assessment period. In group II (n = 5), nitric oxide administration was initiated at the same concentration after reperfusion injury had developed. Group III animals (n = 4) received no nitric oxide. Significant improvement in gas exchange was apparent in group I. At the end of the 6-hour assessment period, mean arterial oxygen tension was 253.8 +/- 44.7 mm Hg and 114.9 +/- 25.5 mm Hg in groups I and III, respectively (p < 0.05). Group II animals had no improvement in oxygenation with nitric oxide. Systemic hemodynamics were unaffected by nitric oxide. However, an immediate

  4. Developmental neurotoxicity of methanol exposure by inhalation in rats.

    Science.gov (United States)

    Weiss, B; Stern, S; Soderholm, S C; Cox, C; Sharma, A; Inglis, G B; Preston, R; Balys, M; Reuhl, K R; Gelein, R

    1996-04-01

    The possibility of widespread methanol exposure via inhalation stemming from its adoption as an automotive fuel or fuel component arouses concerns about the potential vulnerability of the fetal brain. This project was designed to help address such concerns by studying the behavior of neonate and adult rats following perinatal exposure to methanol vapor. Four cohorts of pregnant Long-Evans hooded rats, each cohort consisting of an exposure and a control group, were exposed to 0 parts per million (ppm) (control) or 4,500 ppm methanol vapor for six hours daily beginning on gestation day (GD) 6 with dams and pups then being exposed postnatal day (PND) 21. Exposures took place in 2-m3 Rochester-type inhalation chambers while the animals remained in their plastic breeder cages. Prenatal and postnatal blood methanol concentrations were determined by gas chromatography. Blood methanol concentrations of the dams, measured immediately following a six-hour exposure, were approximately 500 to 800 micrograms/mL throughout gestation and lactation. Average blood methanol concentrations of the pups were about twice those of the dams. Because such results appeared consistently across the other cohorts, we decided to obtain additional data with Cohort 4. Once it had undergone the standard exposure protocol, we selected sets of extra pups from those that had not been assigned previously to the adult phase of behavioral testing. Each set was exposed once, at ages that extended out to PND 52, for one additional six-hour session of exposure to 4,500 ppm methanol. The blood methanol concentrations of these pups declined until about PND 48, at which time they approximated those of the dams. These findings might be accounted for by a process of metabolic maturation in the pups that remains to be identified.

  5. Occupational Exposure to Inhalable Manganese at German Workplaces.

    Science.gov (United States)

    Kendzia, Benjamin; Van Gelder, Rainer; Schwank, Tobias; Hagemann, Cornelia; Zschiesche, Wolfgang; Behrens, Thomas; Weiss, Tobias; Brüning, Thomas; Pesch, Beate

    2017-11-10

    Due to mounting evidence of neurotoxic effects of manganese (Mn) already at low concentrations, occupational exposure limits (OELs) have been adopted. We analyzed 5771 personal measurements of inhalable manganese (Mn) together with information on sampling conditions and job tasks from the German exposure database Messdaten zur Exposition gegenüber Gefahrstoffen am Arbeitsplatz (MEGA) to assess exposure levels in welders and other occupations between 1989 and 2015. Geometric means (GMs) of exposure to Mn were estimated for various occupational settings adjusted for 2-h sampling duration and analytical method, centered at 2009. Measurements below the limit of quantification (LOQ) were multiply imputed. The median concentration was 74 µg m-3 (inter-quartile range 14-260 µg m-3) in welders and 8 µg m-3 (inter-quartile range 100 µg m-3 were observed in gas metal and flux-cored arc welders and in shielded metal arc welders using consumables of high Mn content (>5%). Tungsten inert gas welding, laser welding and working in other occupations such as foundry worker, electroplater, or grinder were associated with GMs <10 µg m-3. A shorter sampling duration was associated with higher Mn concentrations. High-emission welding techniques require protective measures to cope with adopted OELs. Results of this study are useful to assess cumulative Mn exposure in community-based studies on neurotoxic effects. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  6. Nano-liposomal dry powder inhaler of Amiloride Hydrochloride.

    Science.gov (United States)

    Chougule, Mahavir Bhupal; Padhi, Bijay Kumar; Misra, Ambikanandan

    2006-01-01

    The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7.4 containing carriers (lactose/sucrose/mannitol), and glycine as anti-adherent. The resultant dispersion was spray dried. The spray dried powders were characterized and in vitro drug release studies were performed using phosphate buffer saline pH 7.4. In vitro and in vivo drug pulmonary deposition was carried out using Andersen Cascade Impactor and by estimating drug in bronchial alveolar lavage and lung homogenate after intratracheal instillation in rats respectively. Nano-liposomes were found to have mean volume diameter of 198 +/- 15 nm, and 57% +/- 1.9% of drug entrapment. Mannitol based formulation was found to have low density, good flowability, particle size of 6.7 +/- 0.6 microm determined by Malvern MasterSizer, maximum fine particle fraction of 67.6 +/- 0.6%, mean mass aerodynamic diameter 2.3 +/- 0.1 microm, and geometric standard deviation 2.4 +/- 0.1. Developed formulations were found to have prolonged drug release following Higuchi's Controlled Release model and in vivo studies showed maximal retention time of drug of 12 hrs within the lungs and slow clearance from the lungs. This study provides a practical approach for direct lung delivery of Amiloride Hydrochloride encapsulated in liposomes for controlled and prolonged retention at the site of action from dry powder inhaler. It can provide a promising alternative to the presently available nebulizers in terms of prolonged pharmacological effect

  7. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...... not on partial flow-volume curves. Pretreatment with either cimetidine and mepyramine or with indomethacin, did not affect the bronchial obstruction after LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)...

  8. Ex vivo skin absorption of terpenes from Vicks VapoRub ointment.

    Science.gov (United States)

    Cal, Krzysztof; Sopala, Monika

    2008-08-01

    The pharmaceutical market offers a wide range of inhalant drug products applied on the skin that contain essential oils and/or their isolated compounds, i.e. terpenes. Because there are few data concerning the skin penetration of terpenes, especially from complex carriers, the goal of this study was to determine the ex vivo skin absorption kinetics of chosen terpenes, namely eucalyptol, menthol, camphor, alpha-pinene, and beta-pinene, from the product Vicks VapoRub. Human cadaver skin was placed in a flow-through diffusion chamber and the product was applied for 15, 30, and 60 min. After the application time the skin was separated into layers using a tape-stripping technique: three fractions of stratum corneum and epidermis with dermis, and terpenes amounts in the samples were determined by gas-chromatography. The investigated terpenes showed different absorption characteristics related to their physicochemical properties and did not permeate through the skin into the acceptor fluid. Eucalyptol had the largest total accumulation in the stratum corneum and in the epidermis with dermis, while alpha-pinene penetrated into the skin in the smallest amount. The short time in which saturation of the stratum corneum with the terpenes occurred and the high accumulation of most of the investigated terpenes in the skin layers proved that these compounds easily penetrate and permeate the stratum corneum and that in vivo they may easily penetrate into the blood circulation.

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

    Science.gov (United States)

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

    1997-07-01

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

  10. Inhaled medicinal cannabis and the immunocompromised patient.

    Science.gov (United States)

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

    2015-03-01

    Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk.

  11. Insulin inhalation for diabetic patients: Nursing considerations

    Directory of Open Access Journals (Sweden)

    Hanan Mohammed Mohammed

    2016-04-01

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

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

    Science.gov (United States)

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

    2014-08-01

    In the 50 years following the introduction of the first dry powder inhaler to the market, several developments have occurred. Multiple-unit dose and multi-dose devices have been introduced, but first generation capsule inhalers are still widely used for new formulations. Many new particle engineering techniques have been developed and considerable effort has been put in understanding the mechanisms that control particle interaction and powder dispersion during inhalation. Yet, several misconceptions about optimal inhaler performance manage to survive in modern literature. It is, for example still widely believed that a flow rate independent fine particle fraction contributes to an inhalation performance independent therapy, that dry powder inhalers perform best at 4 kPa (or 60 L/min) and that a high resistance device cannot be operated correctly by patients with reduced lung function. Nevertheless, there seems to be a great future for dry powder inhalation. Many new areas of interest for dry powder inhalation are explored and with the assistance of new techniques like computational fluid dynamics and emerging particle engineering technologies, this is likely to result in a new generation of inhaler devices and formulations, that will enable the introduction of new therapies based on inhaled medicines. Copyright © 2014. Published by Elsevier B.V.

  13. Inhaled Nitric Oxide in Acute Lung Disease.

    Science.gov (United States)

    1995-01-01

    progress has been made in im- ONOO- peroxynitrate proving its outcome. Current therapy for the 150,000 PAP pulmonary arterial pressure patients who...documented that LPS ad- relaxation independent of arachidonic acid metabo- ministration resulted in a significant increase in pul- lism. The late phase GBS...true shunt). amounts of NO- entered the circulation (Table 7). The efficacy of inhaled NO. in a porcine oleic acid - Thus, when diffusion is impaired

  14. Electrostatics in pharmaceutical aerosols for inhalation.

    Science.gov (United States)

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

    2013-08-01

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

  15. Gas and Gas Pains

    Science.gov (United States)

    ... Gas and gas pains Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  16. Inhaled dry powder formulations for treating tuberculosis.

    Science.gov (United States)

    Das, Shyamal; Tucker, Ian; Stewart, Peter

    2015-01-01

    Tuberculosis is the second leading cause of death from infectious diseases. Although antitubercular drugs have been traditionally administered orally, there is a growing interest in delivering drugs via the pulmonary route using nebulisers or dry powder inhalers. Drugs in dry powder inhalers (DPI) are stable and DPI are user-friendly compared to nebulisation which is time consuming, inconvenient and inefficient and requires special equipment. For tuberculosis treatment, drugs should target alveolar macrophages that harbour microorganisms and/or maintain high drug concentration at the infection site in the lung. Drug particles include micro-particles or nanoparticles. Powders can be engineered by micronisation, crystallisation, spray drying, freeze drying and particle coating approaches. The formulation may contain single or combination drugs. This paper will provide an update on current status of TB, its pathogenesis, current treatment strategies, shortcomings of current oral or parenteral delivery strategies, pulmonary delivery devices, advantages of pulmonary delivery of powder formulations, formulation approaches and pharmacokinetic studies of pulmonary delivery of powders for inhalation.

  17. Inhalation toxicity of high flash aromatic naphtha.

    Science.gov (United States)

    Clark, D G; Butterworth, S T; Martin, J G; Roderick, H R; Bird, M G

    1989-05-01

    A petroleum distillate--a high aromatic naphtha--consisting of a 50/50 blended mixture of equivalent products. SHELLSOL A* and SOLVESSO 100**, containing C9 isomers (75 percent) particularly trimethyl benzenes, was examined for systemic toxicity in rats by inhalation exposure. A preliminary 13-week inhalation study with SHELLSOL A had resulted in liver and kidney weight increases in female rats at the high (7400 mg/m3) and medium (3700 mg/m3) exposure levels, and a low grade anaemia in females at all exposure levels (7400, 3700 and 1800 mg/m3). The follow-up 12-month inhalation study in rats described here used atmosphere generated from the SHELLSOL A/SOLVESSO 100 blend of 1800, 900 and 450 mg/m3. Initial reduction in body weight gain occurred in both male and female rats at the higher exposures. Various statistically significant haematological changes were transiently seen in males up to six months, but were not considered biologically significant. High exposure male liver and kidney weights were increased at 6 and 12 months but, in the absence of histopathological changes, were considered to be physiological adaptive responses. No treatment-related histopathological abnormalities were found. It is concluded that chronic exposure to this high aromatic naphtha is without systemic toxicity in rats under the conditions of these studies.

  18. Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens.

    Science.gov (United States)

    Luan, Xiaojie; Belev, George; Tam, Julian S; Jagadeeshan, Santosh; Hassan, Noman; Gioino, Paula; Grishchenko, Nikolay; Huang, Yanyun; Carmalt, James L; Duke, Tanya; Jones, Teela; Monson, Bev; Burmester, Monique; Simovich, Tomer; Yilmaz, Orhan; Campanucci, Veronica A; Machen, Terry E; Chapman, L Dean; Ianowski, Juan P

    2017-10-05

    Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR-/- swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.

  19. Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery.

    Science.gov (United States)

    Chen, Rui; Xu, Liu; Fan, Qin; Li, Man; Wang, Jingjing; Wu, Li; Li, Weidong; Duan, Jinao; Chen, Zhipeng

    2017-11-01

    Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC-MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.

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

    Directory of Open Access Journals (Sweden)

    M.D.M. VIANA

    2016-03-01

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

  1. Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler

    OpenAIRE

    Hindle, M.; Peers, E.M.; Parry-Billings, M; CHRYSTYN, H

    1997-01-01

    Aims The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI.

  2. Racemic adrenaline and inhalation strategies in acute bronchiolitis.

    Science.gov (United States)

    Skjerven, Håvard Ove; Hunderi, Jon Olav Gjengstø; Brügmann-Pieper, Sabine Kristin; Brun, Anne Charlotte; Engen, Hanne; Eskedal, Leif; Haavaldsen, Marius; Kvenshagen, Bente; Lunde, Jon; Rolfsjord, Leif Bjarte; Siva, Christian; Vikin, Truls; Mowinckel, Petter; Carlsen, Kai-Håkon; Lødrup Carlsen, Karin C

    2013-06-13

    Acute bronchiolitis in infants frequently results in hospitalization, but there is no established consensus on inhalation therapy--either the type of medication or the frequency of administration--that may be of value. We aimed to assess the effectiveness of inhaled racemic adrenaline as compared with inhaled saline and the strategy for frequency of inhalation (on demand vs. fixed schedule) in infants hospitalized with acute bronchiolitis. In this eight-center, randomized, double-blind trial with a 2-by-2 factorial design, we compared inhaled racemic adrenaline with inhaled saline and on-demand inhalation with fixed-schedule inhalation (up to every 2 hours) in infants (bronchiolitis. An overall clinical score of 4 or higher (on a scale of 0 to 10, with higher scores indicating more severe illness) was required for study inclusion. Any use of oxygen therapy, nasogastric-tube feeding, or ventilatory support was recorded. The primary outcome was the length of the hospital stay, with analyses conducted according to the intention-to-treat principle. The mean age of the 404 infants included in the study was 4.2 months, and 59.4% were boys. Length of stay, use of oxygen supplementation, nasogastric-tube feeding, ventilatory support, and relative improvement in the clinical score from baseline (preinhalation) were similar in the infants treated with inhaled racemic adrenaline and those treated with inhaled saline (P>0.1 for all comparisons). On-demand inhalation, as compared with fixed-schedule inhalation, was associated with a significantly shorter estimated mean length of stay--47.6 hours (95% confidence interval [CI], 30.6 to 64.6) versus 61.3 hours (95% CI, 45.4 to 77.2; P=0.01) - as well as less use of oxygen supplementation (in 38.3% of infants vs. 48.7%, P=0.04), less use of ventilatory support (in 4.0% vs. 10.8%, P=0.01), and fewer inhalation treatments (12.0 vs. 17.0, Pbronchiolitis in infants, inhaled racemic adrenaline is not more effective than inhaled saline

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    The study aimed to investigate dose consistency and particle distribution from the dry powder inhalers Diskus and Turbuhaler. Full profiles of inhalation pressure versus time were recorded in 18 4 yr old and 18 8 yr old asthmatic children through Diskus and Turbuhaler inhalers. These data were used...... represents the changes in flow rate over time through the device than the constant flow rate usually applied with an impactor alone. The aerosol cloud was released before the peak inspiratory effort had been achieved and accordingly the early part and not the peak of the inspiratory performance...... the varying age groups and inspiratory flow performances when compared to the Turbuhaler in terms of the proportion of the dose emitted at each particle size. This improvement is at the expense of a low fine particle mass and a high proportion of coarse particles from the Diskus as compared...

  4. Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.

    Science.gov (United States)

    Adams, Wallace P; Ahrens, Richard C; Chen, Mei-Ling; Christopher, David; Chowdhury, Badrul A; Conner, Dale P; Dalby, Richard; Fitzgerald, Kevin; Hendeles, Leslie; Hickey, Anthony J; Hochhaus, Günther; Laube, Beth L; Lucas, Paul; Lee, Sau L; Lyapustina, Svetlana; Li, Bing; O'Connor, Dennis; Parikh, Neil; Parkins, David A; Peri, Prasad; Pitcairn, Gary R; Riebe, Michael; Roy, Partha; Shah, Tushar; Singh, Gur Jai Pal; Sharp, Sandra Suarez; Suman, Julie D; Weda, Marjolein; Woodcock, Janet; Yu, Lawrence

    2010-02-01

    This March 2009 Workshop Summary Report was sponsored by Product Quality Research Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS). Participants from the pharmaceutical industry, academia and regulatory bodies from the United States, Europe, India, and Brazil attended the workshop with the objective of presenting, reviewing, and discussing recommendations for demonstrating bioequivalence (BE) that may be considered in the development of orally inhaled drug products and regulatory guidances for new drug applications (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop addressed areas related to in vitro approaches to demonstrating BE, biomarker strategies, imaging techniques, in vivo approaches to establishing local delivery equivalence and device design similarity. The workshop presented material that provided a baseline for the current understanding of orally inhaled drug products (OIPs) and identified gaps in knowledge and consensus that, if answered, might allow the design of a robust, streamlined method for the BE assessment of locally acting inhalation drugs. These included the following: (1) cascade impactor (CI) studies are not a good 2 predictor of the pulmonary dose; more detailed studies on in vitro/in vivo correlations (e.g., suitability of CI studies for assessing differences in the regional deposition) are needed; (2) there is a lack of consensus on the appropriate statistical methods for assessing in vitro results; (3) fully validated and standardized imaging methods, while capable of providing information on pulmonary dose and regional deposition, might not be applicable to the BE of inhaled products mainly due to the problems of having access to radiolabeled innovator product; (4) if alternatives to current methods for establishing local delivery BE of OIPs cannot be established, biomarkers (pharmacodynamic or clinical

  5. Powder Production and Particle Engineering for Dry Powder Inhaler Formulations.

    Science.gov (United States)

    Lin, Yu-Wei; Wong, Jennifer; Qu, Li; Chan, Hak-Kim; Zhou, Qi Tony

    2015-01-01

    Dry powder inhalers have become increasingly attractive for pulmonary delivery of locally and systemically effective medications. In comparison to the liquid counterparts, such as nebulisation and pressurised metered dose inhalers, the powder form generally offers better chemical stability, improved portability and potentially superior patient adherence. Currently, the aerosol performance between dry powder inhalers varies to a large extent due to differences in the design of inhaler device and formulation. The particulate properties have a significant influence on the inter-particle interactions, which impacts on the aerosolisation of the inhaled powder. In this review, critical particulate properties that affect aerosol performance are discussed. Recent advances in powder production and particle engineering techniques are also assessed, aiming to develop new inhaled powder formulations or improve the aerosolisation efficiency of existing products.

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

    Science.gov (United States)

    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 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 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.

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

    DEFF Research Database (Denmark)

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

    2009-01-01

    review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics......In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we...

  8. Pharmacokinetics and pharmacodynamics of fluticasone propionate and salmeterol delivered as a combination dry powder from a capsule-based inhaler and a multidose inhaler in asthma and COPD patients.

    Science.gov (United States)

    Daley-Yates, Peter T; Mehta, Rashmi; Chan, Robert H; Despa, Simona X; Louey, Margaret D

    2014-08-01

    The object of this study was to assess whether a capsule-based and multidose dry powder inhaler containing salmeterol (as xinafoate salt) 50 μg plus fluticasone propionate (FP) 250 μg [combination (SFC 50/250)] could be equivalent in terms of in vivo drug delivery and systemic exposure. This was a randomized, double-blind, double-dummy, replicate treatment design comparative bioavailability study of SFC 50/250 delivered in a capsule-based inhaler (Rotahaler®) and a multidose dry powder inhaler (Diskus®). Subjects with asthma or chronic obstructive pulmonary (COPD) disease (n=60) were randomized to receive twice-daily SFC 50/250 via a Rotahaler and via Diskus each for two 10-day treatment periods (GlaxoSmithKline Protocol ASR114334). For FP and salmeterol, the in vitro aerodynamic particle size profiles were within±15% of Diskus for the fine particle mass (FPM) and emitted dose (ED) using the Andersen Cascade Impactor, and ED, mass median aerodynamic diameter, and geometric standard deviation using the New Generation Impactor (NGI). This was also the case for FP but not salmeterol for FPM and fine particle dose using the NGI. For the combined asthma and COPD subjects, the plasma AUC and Cmax for FP and salmeterol were higher for Rotahaler:Rotahaler/Diskus geometric mean ratios (90% confidence intervals) for FP AUC0-τ of 1.52 (1.37-1.67) and Cmax of 1.94 (1.75-2.10) and salmeterol AUC0-τ of 1.15 (1.09-1.21) and Cmax of 1.56 (1.42-1.67). Corresponding values for the primary pharmacodynamic endpoint, weighted mean (0-12 hr) serum cortisol, were 0.928 (0.886-0.971). Inhaled FP/salmeterol via both inhalers was well-tolerated. One serious adverse event, considered possibly related to study medication, resulted in subject withdrawal from the study. The in vitro tests and systemic pharmacodynamic endpoints revealed no major differences between the two inhalers, but lacked predictive power and sensitivity to guide in vivo drug delivery performance and systemic

  9. Need for a comparative performance standard for dry powder inhalers.

    Science.gov (United States)

    Richards, R.; Saunders, M.

    1993-01-01

    The efficacy of dry powder inhalers is dependent on the inspiratory flow rate at which they are used. The resistance to airflow through five different dry powder inhaler devices was measured. The devices were shown to vary significantly, with the Turbohaler having the highest resistance. We suggest that the performance of dry powder inhalers should be assessed at comparable pressure drops producing clinically relevant inspiratory flow rates for each device. Images PMID:8296270

  10. In vivo

    Science.gov (United States)

    Berkowitz, Bruce A; Lenning, Jacob; Khetarpal, Nikita; Tran, Catherine; Wu, Johnny Y; Berri, Ali M; Dernay, Kristin; Haacke, E Mark; Shafie-Khorassani, Fatema; Podolsky, Robert H; Gant, John C; Maimaiti, Shaniya; Thibault, Olivier; Murphy, Geoffrey G; Bennett, Brian M; Roberts, Robin

    2017-09-01

    Hippocampus oxidative stress is considered pathogenic in neurodegenerative diseases, such as Alzheimer disease (AD), and in neurodevelopmental disorders, such as Angelman syndrome (AS). Yet clinical benefits of antioxidant treatment for these diseases remain unclear because conventional imaging methods are unable to guide management of therapies in specific hippocampus subfields in vivo that underlie abnormal behavior. Excessive production of paramagnetic free radicals in nonhippocampus brain tissue can be measured in vivo as a greater-than-normal 1/ T 1 that is quenchable with antioxidant as measured by quench-assisted (Quest) MRI. Here, we further test this approach in phantoms, and we present proof-of-concept data in models of AD-like and AS hippocampus oxidative stress that also exhibit impaired spatial learning and memory. AD-like models showed an abnormal gradient along the CA1 dorsal-ventral axis of excessive free radical production as measured by Quest MRI, and redox-sensitive calcium dysregulation as measured by manganese-enhanced MRI and electrophysiology. In the AS model, abnormally high free radical levels were observed in dorsal and ventral CA1. Quest MRI is a promising in vivo paradigm for bridging brain subfield oxidative stress and behavior in animal models and in human patients to better manage antioxidant therapy in devastating neurodegenerative and neurodevelopmental diseases.-Berkowitz, B. A., Lenning, J., Khetarpal, N., Tran, C., Wu, J. Y., Berri, A. M., Dernay, K., Haacke, E. M., Shafie-Khorassani, F., Podolsky, R. H., Gant, J. C., Maimaiti, S., Thibault, O., Murphy, G. G., Bennett, B. M., Roberts, R. In vivo imaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome. © FASEB.

  11. Corticosteroid inhalation in the treatment of childhood asthma.

    Science.gov (United States)

    Munasir, Z; Knol, K

    1990-01-01

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

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

    Science.gov (United States)

    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.

  13. The dispersion behaviour of dry powder inhalation formulations cannot be assessed at a single inhalation flow rate.

    Science.gov (United States)

    Grasmeijer, Floris; de Boer, Anne H

    2014-04-25

    The dispersion performances of inhalation powders are often tested at only one inhalation flow rate in mechanistic formulation studies. This limited approach is challenged by studies showing that interactions exist between inhalation flow rate and the effects on dispersion performance of several formulation variables. In this note we explain that such interactions with inhalation flow rate are, in fact, always to be expected. Because these interactions may greatly affect conclusions concerning the effects of formulation variables and their underlying mechanisms, the utility of future dry powder inhalation formulation studies may benefit from an approach in which dispersion performance is by default tested over a range of inhalation flow rates. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals

    Directory of Open Access Journals (Sweden)

    Unfried K

    2016-10-01

    Full Text Available Klaus Unfried,1,* Ursula Krämer,1,* Ulrich Sydlik,1 Andrea Autengruber,1 Andreas Bilstein,2 Sabine Stolz,1 Alessandra Marini,1 Tamara Schikowski,1 Stefanie Keymel,3 Jean Krutmann1 1IUF Leibniz Research Institute of Environmental Medicine, 2bitop AG, Witten, 3Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany *These authors contributed equally to this work Background: Compatible solutes are natural substances that are known to stabilize cellular functions. Preliminary ex vivo and in vivo studies demonstrated that the compatible solute ectoine restores natural apoptosis rates of lung neutrophils and contributes to the resolution of lung inflammation. Due to the low toxicity and known compatibility of the substance, an inhalative application as an intervention strategy for humans suffering from diseases caused by neutrophilic inflammation, like COPD, had been suggested. As a first approach to test the feasibility and efficacy of such a treatment, we performed a population-based randomized trial.Objective: The objective of the study was to test whether the daily inhalation of the registered ectoine-containing medical device (Ectoin® inhalation solution leads to a reduction of neutrophilic cells and interleukin-8 (IL-8 levels in the sputum of persons with mild symptoms of airway disease due to lifelong exposure to environmental air pollution.Methods: A double-blinded placebo-controlled trial was performed to study the efficacy and safety of an ectoine-containing therapeutic. Prior to and after both inhalation periods, lung function, inflammatory parameters in sputum, serum markers, and quality-of-life parameters were determined.Results: While the other outcomes revealed no significant effects, sputum parameters were changed by the intervention. Nitrogen oxides (nitrate and nitrite were significantly reduced after ectoine inhalation with a mean quotient of 0.65 (95% confidence

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

    Directory of Open Access Journals (Sweden)

    Richard Hodder

    2009-10-01

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

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

    Science.gov (United States)

    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.

  17. Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis.

    Science.gov (United States)

    Majoral, Caroline; Fleming, John; Conway, Joy; Katz, Ira; Tossici-Bolt, Livia; Pichelin, Marine; Montesantos, Spyridon; Caillibotte, Georges

    2014-10-01

    To provide a validation dataset for aerosol deposition modeling, a clinical trial was performed in which the inhalation parameters and the inhaled aerosol were controlled or characterized. Eleven, healthy, never-smokers, male participants completed the study. Each participant performed two inhalations of (99m)Tc-labeled aerosol from a vibrating mesh nebulizer, which differed by a single controlled parameter (aerosol particle size: "small" or "large"; inhalation: "deep" or "shallow"; carrier gas: air or a helium-oxygen mix). The deposition measurements were made by planar imaging, and single photon emission computed tomography-computed tomography (SPECT-CT). The difference between the mean activity measured by two-dimensional imaging and that delivered from the nebulizer was 2.7%, which was not statistically significant. The total activity deposited was significantly lower in the left lung than in the right lung (p<0.0001) with a mean ratio (left/right) of 0.87±0.1 standard deviation (SD). However, when normalized to lung air volume, the left lung deposition was significantly higher (p=0.0085) with a mean ratio of 1.08±0.12 SD. A comparison of the three-dimensional central-to-peripheral (nC/P3D) ratio showed that it was significantly higher for the left lung (p<0.0001) with a mean ratio (left/right) of 1.36±0.20 SD. The effect of particle size was statistically significant on the nC/P3D ratio (p=0.0014), extrathoracic deposition (p=0.0037), and 24-hr clearance (p<0.0001), contrary to the inhalation parameters, which showed no effect. This article presents the results of an analysis of the in vivo deposition data, obtained in a clinical study designed to provide data for model validation. This study has demonstrated the value of SPECT imaging over planar, the influence of particle size on regional distribution within the lung, and differences in deposition between the left and right lungs.

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

    NARCIS (Netherlands)

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

    In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we

  19. Genuair® in chronic obstructive pulmonary disease: a novel, user-friendly, multidose, dry-powder inhaler

    NARCIS (Netherlands)

    van der Palen, Jacobus Adrianus Maria

    2014-01-01

    Inhaled corticosteroids and bronchodilators, which are pivotal to the management of respiratory diseases, are delivered by numerous devices, including pressurized metered-dose inhalers and dry-powder inhalers. However, patient adherence to these medications is suboptimal and incorrect inhaler

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

    Science.gov (United States)

    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.

  1. Traumatic Inhalation due to Merapi Volcanic Ash

    Directory of Open Access Journals (Sweden)

    Ika Trisnawati

    2016-05-01

    note, diminished vesicular breath sounds in lower right side of the chest. The chest X-ray presence leads to bleb. Based on the clinical and radiological suspicion of pneumoconiosis the patient was submitted to computed tomography of the chest and revealed bilateral multiple bullae mainly at the right lung field. The biopsy specimen verified the diagnosis of anthrocosilicosis. There is no proven specific therapy for any form of silicosis. Symptomatic therapy should include treatment of airflow limitation with bronchodilators, aggressive management of respiratory tract infection with antibiotics, and use of supplemental oxygen (if indicated toprevent complications of chronic hypoxemia. Key words: Pneumonoultramicroscopicsilicovolcanoconiosis, inorganic particles inhalation, dyspnoea, bullae.

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

    Science.gov (United States)

    2010-01-01

    Background We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 ± 5 nm; 0.12 ± 0.03 mg/m3; 6 hours/days for 5 days/week) for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs) were examined in rat lungs in both studies. Results In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2αβ and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2αβ and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2αβ and-3 in the fullerene group. Conclusion These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation. PMID:20226088

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

    Directory of Open Access Journals (Sweden)

    Yamamoto Kazuhiro

    2010-03-01

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

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

    OpenAIRE

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

    1990-01-01

    The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelle...

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

    National Research Council Canada - National Science Library

    Fink, James B

    2012-01-01

    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...

  6. Unintended effects of inhaled corticosteroids : disease or drugs?

    NARCIS (Netherlands)

    Vries, F. de

    2007-01-01

    Patients with asthma or COPD are often treated with inhaled corticosteroids. These drugs reduce the inflammation in the lungs and patients suffer fewer exacerbations. In the late nineties, a tendency to treat patients in general with higher doses of inhaled corticosteroids was accompanied with an

  7. Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

    African Journals Online (AJOL)

    Background: An Adequate and an effective dose of inhalation drugs can be administered only if the correct inhaler‑specific technique is followed by asthma patients. There is paucity of data on this subject among Nigerians and Africans. Aims: This observational study was to assess the inhaler techniques among asthma ...

  8. [The choice of inhalation device: A medical act].

    Science.gov (United States)

    Devillier, P; Salvator, H; Roche, N

    2015-06-01

    Inhaled treatments are essential for respiratory diseases management, including COPD and asthma. Optimal control of the disease largely depends on patient's compliance and proper use of these treatments. Different types of ready-to-use inhaler devices are available: metered dose inhaler, dry powder inhaler or soft mist inhaler. Each of these devices presents specific characteristics and constraints that have to be evaluated and taken into account before prescription. In order to optimize adherence and treatment efficacy, the choice of inhaler device should depend on the specific needs, abilities and preferences of each patient and a specific education to treatment should be provided. Inhaled treatments, even containing the same drug, have different technical constraints and are thus not easily interchangeable. Their substitution without prior medical consent and without proper training can lead to errors in taking treatment, treatment failures and increased health care consumption. In France, substitution by the pharmacist is not authorized. While patient education must be carried out in collaboration with all health professionals, it is preferable that the choice of inhaler device remains the responsibility of the physician. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  9. The formulation and evaluation of salbutamol dry powder inhalation ...

    African Journals Online (AJOL)

    Metered dose inhalers (MDIs) contain chlorofluorocarbons, widely known, to affect the environment adversely. These chemicals deplete the ozone layer. The use of dry powder inhalers is therefore in the ascendance to replace MDIs for delivery of medicines to the respiratory tract. In this study we have formulated dry powder ...

  10. Education on Correct Inhaler Technique in Pharmacy Schools ...

    African Journals Online (AJOL)

    Purpose: To investigate the effectiveness of a standard educational module on pharmacy students' inhaler technique demonstration skills. Methods: This investigational study was conducted during the Clinical Pharmacy and Therapeutics tutorial classes in 2011. All fifth-year students were given placebo inhaler devices and ...

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  12. Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

    African Journals Online (AJOL)

    hanumantp

    Department of Medicine, Respiratory Unit, College of Medicine, University of Nigeria, Enugu Campus, Enugu,. 1Department of Medicine ... factors related to an inaccurate or poor inhaler use. Subjects and ... likely to use the pMDI inhalers more accurately while patients who have been taught previously by a Doctor were ...

  13. Conference report: 1st Medicon Valley Inhalation Symposium.

    Science.gov (United States)

    Lastow, Orest

    2013-02-01

    The 1st Medicon Valley Inhalation Symposium was arranged by the Medicon Valley Inhalation Consortium. It was held at the Medicon Village site, which is the former AstraZeneca site in Lund, Sweden. It was a 1-day symposium focused on inhaled drug delivery and inhalation product development. A total of 90 delegates listened to 15 speakers. The program was organized to follow the value chain of an inhalation product development. The benefits and future opportunities of inhaled drug delivery were discussed together with some new disease areas that can be targeted with inhalation. The pros and cons of the two main formulation types; dry powder and liquid formulations, were discussed by a panel. The different requirements of the drug molecules from a pharmacology, chemical and physical perspective were explained. The modeling of the physics inside an inhaler was demonstrated and the potential strategic benefits of device design were highlighted together with the many challenges of formulation manufacturing. Lung deposition mechanisms and the difficulties of the generic bioequivalence concept were discussed. Using an anatomically correct impactor inlet is a valuable tool in lung deposition predictions and the planning of clinical trials. The management of the biological material generated in clinical studies is key to successful studies.

  14. Education on Correct Inhaler Technique in Pharmacy Schools ...

    African Journals Online (AJOL)

    Purpose: To investigate the effectiveness of a standard educational module on pharmacy students' inhaler technique demonstration ... addition, students' perceived barriers to demonstrating correct use of ..... demonstrating their correct use following in class education on correct inhaler technique. Frequency (%) Identified ...

  15. Inhalation characteristics and their effects on in vitro drug delivery from dry powder inhalers .1. Inhalation characteristics, work of breathing and volunteers' preference in dependence of the inhaler resistance

    NARCIS (Netherlands)

    deBoer, AH; Winter, H.M.I.; Lerk, CF

    1996-01-01

    A test inhaler with exchangeable air flow resistances encompassing the range of commercial DPIs has been used to study the inspiratory flow curves of 39 healthy adult volunteers. A strong increase in mean Peak Inspiratory Flow Rate (PIFR) has been obtained with decreasing inhaler resistance, varying

  16. Alveolar proteinosis associated with aluminium dust inhalation.

    Science.gov (United States)

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Recent patents in pressurised metered dose inhalers.

    Science.gov (United States)

    Ehtezazi, Touraj

    2012-04-01

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

  18. Inhalation Exposure Method for Illegal Drugs.

    Science.gov (United States)

    Inomata, Akiko; Ogata, Akio; Tada, Yukie; Nagasawa, Akemichi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Takahashi, Hiroshi; Kaihoko, Fujifumi; Tanaka, Kazuyoshi; Nakajima, Jun'ichi; Suzuki, Atsuko; Uemura, Nozomi; Moriyasu, Takako; Watanabe, Daisuke; Ishihara, Kei; Usami, Takashi; Kamei, Satoru; Kohno, Yasuaki

    2017-01-01

    We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product "SOUTOU" containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control.

  19. Formulation Design of Dry Powders for Inhalation.

    Science.gov (United States)

    Weers, Jeffry G; Miller, Danforth P

    2015-10-01

    Drugs for inhalation are no longer exclusively highly crystalline small molecules. They may also be amorphous small molecules, peptides, antibodies, and myriad types of engineered proteins. The evolution of respiratory therapeutics has created a need for flexible formulation technologies to engineer respirable particles. These technologies have enabled medicinal chemists to focus on molecular design without concern regarding compatibility of physicochemical properties with traditional, blend-based technologies. Therapeutics with diverse physicochemical properties can now be formulated as stable and respirable dry powders. Particle engineering technologies have also driven the deployment of new excipients, giving formulators greater control over particle and powder properties. This plays a key role in enabling efficient delivery of drugs to the lungs. Engineered powder and device combinations enable aerosols that largely bypass the mouth and throat, minimizing the inherent variability among patients that arises from differences in oropharyngeal and airway anatomies and in breathing profiles. This review explores how advances among molecules, particles, and powders have transformed inhaled drug product development. Ultimately, this scientific progress will benefit patients, enabling new classes of therapeutics to be formulated as dry powder aerosols with improved efficacy, reduced variability and side effects, and improved patient adherence. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. [Esophageal candidiasis as complication of inhaled steroid therapy].

    Science.gov (United States)

    Shuto, Hiroshi; Nagata, Makoto; Terashi, Yoshinori; Yamaguchi, Michiya; Takizawa, Takao; Shuto, Chizuru; Watanabe, Kensuke; Tosaka, Kaoru; Okano, Masahiko; Noguchi, Hisashi

    2003-11-01

    Gastrointestinal endoscopy was performed in two bronchial asthma patients using inhaled corticosteroid who complained of odynophagia. The endoscopic finding was high grade with white moss (Grade III) in both patients. Esophageal candidiasis is often recognized in bronchial asthmatic patients receiving long-term fluticasone propionate (FP) dry powder (Diskhaler) inhalation. We therefore examined the complicated context of esophageal candidiasis in patients with long-term FP inhalation. Out of 20 bronchial asthmatic patients who had been using FP inhalation long-term, seven showed signs of esophageal candidiasis. Three patients had mild grade (Grade I), one middle grade (Grade II) and three high grade (Grade III) candidiasis, with a frequency of 35%. This rate is higher than the usual spontaneous occurrence rate of esophageal candidiasis, and it is suggested that inhalation of corticosteroid medication can penetrate into the esophagus after deep inhalation. We tested this hypothesis in two studies. 1) To measure the esophageal concentration of FP, four healthy adults inhaled 200 microg FP once. Right after inhalation, FP concentration in the esophageal washing fluid was 3.3 microg. On another day, 30 minutes after the same dose of inhaled FP, one FP concentration in the esophageal washing fluid was 0.67 microg (immediately laydown), and another was 0.11 microg (remained standing). This indicates that even though FP dissipates quickly, it remains in the esophagus 30 minutes after inhalation. 2) We observed the process in one patient with high grade (Grade III) esophageal candidiasis. The time of inhalation was changed from just after getting up and just before going to bed to before breakfast and before dinner. Under this regimen, the signs of esophageal candidiasis improved from high to middle grade. If asthmatic patients do not go to sleep immediately after FP inhalation, the remaining FP in the esophagus decreases rapidly, thereby decreasing the risk of esophageal

  1. SIXTY YEARS AFTER INHALATIONAL DEVICES- WHERE DO WE STAND?

    Directory of Open Access Journals (Sweden)

    Jayasri Helen Gali

    2017-01-01

    Full Text Available BACKGROUND Bronchial asthma and chronic obstructive pulmonary disease are the Common Respiratory Diseases (CRD’s. Drugs delivered through inhaler devices are the backbone for treatment of CRD’s. Inhaler technique errors are common even after more than 60 years of introduction of these devices. The aim of the study is to explore the faulty inhaler techniques among patients with asthma and chronic obstructive pulmonary diseases. Health education has significant impact on improving the inhaler technique thereby achieving better disease control and also brings out regularity of inhaler usage by patients. MATERIALS AND METHODS All the relevant information including patients profile and usage of inhalers was collected by a prepared questionnaire from 242 patients with asthma or COPD attending our OPD. The patient’s inhaler technique was assessed using a standard checklist for proper use of a Metered-Dose Inhaler (MDI or Dry Powder Inhaler (DPI. All the participants were asked to demonstrate their inhaler technique, which was assessed and documented. Education was given to all patients about the correct inhalational method and they were also counseled to adhere to it. Inhaler technique was reassessed in all the patients after a month and reinforcement of the correct technique was done. Statistical Analysis- Using the chi-square test, P-values of each variable like age, gender, education, duration of illness, etc. were derived. P value of less than 0.05 was considered significant. Settings and Design- This is a cross-sectional study with an interventional component done on 242 patients with bronchial asthma or COPD attending the pulmonology OPD in Apollo Institute of Medical Sciences and Research. RESULTS Out of 242 patients studied on baseline evaluation in the first visit, only 46 patients (19.008% were able to do the technique correctly, which after education on the correct inhaler technique increased to 134 patients (55.37% in the follow up

  2. Inhaled antibiotics for gram-negative respiratory infections.

    Science.gov (United States)

    Hudson, Ryan; Olson Blair, Brooke

    2011-10-01

    Several disease states create conditions that lead to opportunistic Gram-negative respiratory infections. Inhalation is the most direct and, until recently, underutilized means of antimicrobial drug targeting for respiratory tract infections. All approved antimicrobial agents for administration by inhalation are indicated for Pseudomonas aeruginosa infections in patients with cystic fibrosis. These inhaled therapies have directly contributed to a significant reduction in exacerbations and hospitalizations in this patient population over the last few decades. The relentless adaptation of pathogenic organisms to current treatment options demands that the pharmaceutical industry continue designing next-generation antimicrobial agents over 70 years after they were first introduced. Recent technological advances in inhalation devices and drug formulation techniques have broadened the scope of antimicrobial structural classes that can be investigated by inhalation; however, there is an urgent need to discover novel compounds with improved resistance profiles relative to those drugs that are already marketed.

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

    DEFF Research Database (Denmark)

    Krogh, Nanna; Rzeppa, Sebastian; Dyreborg, Anders

    2017-01-01

    PURPOSE: This study investigated pharmacokinetics of terbutaline after single and seven consecutive days of inhalation in exercising trained men. METHODS: Twelve healthy young trained men underwent two pharmacokinetic trials comparing single dose (2 mg) and seven consecutive days (2 mg×d) of inha......PURPOSE: This study investigated pharmacokinetics of terbutaline after single and seven consecutive days of inhalation in exercising trained men. METHODS: Twelve healthy young trained men underwent two pharmacokinetic trials comparing single dose (2 mg) and seven consecutive days (2 mg......×d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high...

  4. Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges.

    Science.gov (United States)

    Haque, Shadabul; Whittaker, Michael R; McIntosh, Michelle P; Pouton, Colin W; Kaminskas, Lisa M

    2016-08-01

    The inhaled delivery of nanomedicines can provide a novel, non-invasive therapeutic strategy for the more localised treatment of lung-resident diseases and potentially also enable the systemic delivery of therapeutics that are otherwise administered via injection alone. However, the clinical translation of inhalable nanomedicine is being hampered by our lack of understanding about their disposition and clearance from the lungs. This review provides a comprehensive overview of the biodegradable nanomaterials that are currently being explored as inhalable drug delivery systems and our current understanding of their disposition within, and clearance from the lungs. The safety of biodegradable nanomaterials in the lungs is discussed and latest updates are provided on the impact of inflammation on the pulmonary pharmacokinetics of inhaled nanomaterials. Overall, the review provides an in-depth and critical assessment of the lung clearance mechanisms for inhaled biodegradable nanomedicines and highlights the opportunities and challenges for their translation into the clinic. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Design and evaluation of a new dry powder inhaler

    Directory of Open Access Journals (Sweden)

    "Rouholamini Najafabadi AH

    2001-08-01

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

  6. Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Bayat, S. [TIMC-PRETA, UMR CNRS 5525, Laboratoire de Physiologie, Universite Joseph Fourier, Faculte de Medecine, Domaine de la Merci, Grenoble (France)]. E-mail: sam.bayat@imag.fr; Le Duc, G.; Berruyer, G.; Nemoz, C.; Monfraix, S.; Fiedler, S.; Thomlinson, W. [European Synchrotron Radiation Facility, BP 220, Grenoble (France); Porra, L.; Suortti, P. [Department of Physics, University of Helsinki, Helsinki (Finland); Standertskjoeld-Nordenstam, C.G. [Department of Radiology, University of Helsinki Central Hospital, Helsinki (Finland); Sovijaervi, A.R.A. [Department of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki (Finland)

    2001-12-01

    Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter. (author)

  7. Does Inhalation of Virgin Coconut Oil Accelerate Reversal of Airway Remodelling in an Allergic Model of Asthma?

    Directory of Open Access Journals (Sweden)

    N. A. Kamalaldin

    2017-01-01

    Full Text Available Many studies have been done to evaluate the effect of various natural products in controlling asthma symptoms. Virgin coconut oil (VCO is known to contain active compounds that have beneficial effects on human health and diseases. The objective of this study was to evaluate the effect of VCO inhalation on airway remodelling in a rabbit model of allergic asthma. The effects of VCO inhalation on infiltration of airway inflammatory cells, airway structures, goblet cell hyperplasia, and cell proliferation following ovalbumin induction were evaluated. Allergic asthma was induced by a combination of ovalbumin and alum injection and/or followed by ovalbumin inhalation. The effect of VCO inhalation was then evaluated via the rescue or the preventive route. Percentage of inflammatory cells infiltration, thickness of epithelium and mucosa regions, and the numbers of goblet and proliferative cells were reduced in the rescue group but not in preventive group. Analysis using a gas chromatography-mass spectrometry found that lauric acid and capric acid were among the most abundant fatty acids present in the sample. Significant improvement was observed in rescue route in alleviating the asthma symptoms, which indicates the VCO was able to relieve asthma-related symptoms more than preventing the onset of asthma.

  8. [Inhalation exposure to welding fumes of arc welders in processing Cr-Ni steel in large chemical industry].

    Science.gov (United States)

    Dyrba, B C; Richter, K H

    1989-05-01

    For clearing up the inhalative load by welding fumes and gases of arc welders in industrial workshops mainly working on Cr-Ni-steels the following welding processes were studied: tungsten inert-gas (TIG), electrode-by-hand (EH), metal inert-gas (MIG), and plasma cutting (plasma). From the total load by welding fumes follows the rank TIG less than EH less than plasma less than MIG. Observing the maximum allowable concentration (MACD) for the total welding fume, no MACD for Cr and Ni was found exceeded. Regarding the welding gases ozone and CO no limit values were exceeded. From the results conclusions were made.

  9. Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler.

    Science.gov (United States)

    Selroos, O; Halme, M

    1991-01-01

    BACKGROUND: High doses of inhaled corticosteroids are absorbed systemically and may cause long term side effects. As rinsing the mouth out after use and inhaling through a spacing device may reduce systemic absorption this has been further investigated. METHODS: Three crossover studies were carried out to assess the effect of budesonide given by dry powder inhaler (Turbuhaler) with and without mouth rinsing and beclomethasone dipropionate given by metered dose inhaler with or without a spacing device (Volumatic) on serum cortisol concentrations and urinary cortisol excretion in patients with asthma taking an inhaled corticosteroid. Each treatment period was two weeks with in a two week washout period. Serum cortisol concentrations at 0800 hours on day 14 and the 24 hour urinary excretion of cortisol were measured. In study 1 24 patients taking beclomethasone dipropionate 500 micrograms twice a day inhaled with (n = 10) or without (n = 14) a Volumatic spacing device were switched to a budesonide dry powder inhaler, 600 micrograms to be taken twice a day without mouth rinsing. In study 2 10 patients took budesonide 800 micrograms twice a day with and without mouth rinsing and without swallowing the rinsing water. In study 3 17 patients took budesonide 800 micrograms twice daily with mouth rinsing and beclomethasone dipropionate 500 micrograms twice daily with the spacing device and mouth rinsing. RESULTS: In study 1 no difference was seen between budesonide without mouth rinsing and beclomethasone dipropionate without a spacer: beclomethasone with spacer caused less suppression of cortisol (mean (SD) serum cortisol concentration: beclomethasone and spacer 487(148), budesonide 368(145) nmol/l). In study 2 mouth rinsing caused less suppression of morning serum cortisol concentrations (rinsing 440(63), no rinsing 375(56) nmol/1). In study 3 there was no difference in serum or urinary cortisol concentrations between twice daily beclomethasone dipropionate 500 micrograms

  10. Validating CFD Predictions of Pharmaceutical Aerosol Deposition with In Vivo Data.

    Science.gov (United States)

    Tian, Geng; Hindle, Michael; Lee, Sau; Longest, P Worth

    2015-10-01

    CFD provides a powerful approach to evaluate the deposition of pharmaceutical aerosols; however, previous studies have not compared CFD results of deposition throughout the lungs with in vivo data. The in vivo datasets selected for comparison with CFD predictions included fast and slow clearance of monodisperse aerosols as well as 2D gamma scintigraphy measurements for a dry powder inhaler (DPI) and softmist inhaler (SMI). The CFD model included the inhaler, a characteristic model of the mouth-throat (MT) and upper tracheobronchial (TB) airways, stochastic individual pathways (SIPs) representing the remaining TB region, and recent CFD-based correlations to predict pharmaceutical aerosol deposition in the alveolar airways. For the monodisperse aerosol, CFD predictions of total lung deposition agreed with in vivo data providing a percent relative error of 6% averaged across aerosol sizes of 1-7 μm. With the DPI and SMI, deposition was evaluated in the MT, central airways (bifurcations B1-B7), and intermediate plus peripheral airways (B8 through alveoli). Across these regions, CFD predictions produced an average relative error <10% for each inhaler. CFD simulations with the SIP modeling approach were shown to accurately predict regional deposition throughout the lungs for multiple aerosol types and different in vivo assessment methods.

  11. An in vitro approach to assess the toxicity of inhaled tobacco smoke components: nicotine, cadmium, formaldehyde and urethane.

    Science.gov (United States)

    Balharry, Dominique; Sexton, Keith; BéruBé, Kelly A

    2008-02-03

    One of the first lines of defence to inhaled toxins is the barrier formed by the tracheobronchial epithelium, making this the ideal region for studying the toxicity of inhaled substances. This study utilises a highly differentiated, three-dimensional, in vitro model of human upper respiratory tract epithelium (EpiAirway-100) to measure the acute toxicological responses to well-characterised tobacco smoke components. To determine the suitability of this model for screening inhaled toxicants, the EpiAirway tissue model (ETM) was treated apically with tobacco smoke components (nicotine, formaldehyde, cadmium, urethane) which are known to induce a variety of toxic effects (e.g. cytotoxic, thrombogenic, carcinogenic). A range of concentrations were used to model different mechanisms and severity of toxicity which were then compared to known in vivo responses. Similar trends in stress response occurred, with distinct alterations to the tissue in response to all four toxins. At high concentrations, cell viability decreased and tight junctions were degraded, but at sub-toxic concentrations epithelial resistance (indicating tissue integrity) increased 20-60% from control. This peak in resistance coincided with an increase in secreted protein levels, elevated cytokine release and goblet cell hyperplasia and hypertrophy. In conclusion, acute exposure to tobacco smoke components induces measurable toxic responses within human respiratory epithelium. Sub-toxic concentrations appear to illicit a protective response by increasing mucus secretion and mediating immune responses via cytokine release. These responses are comparable to human in vivo responses, indicating potential for the ETM as a tool for screening the toxicity of inhaled compounds.

  12. Frequency distribution of gastro esophageal reflux disease in inhalation injury: A historical cohort study

    Directory of Open Access Journals (Sweden)

    Ashraf Karbasi

    2015-01-01

    Full Text Available Background: There is no data on the prevalence and the association of gastro esophageal reflux disease (GERD with toxic fume inhalation. Therefore, we aimed to evaluate the frequency distribution of GERD symptoms among the individuals with mild respiratory disorder due to the past history of toxic fume exposure to sulfur mustard (SM. Materials and Methods: In a historical cohort study, subjects were randomly selected from 7000 patients in a database of all those who had a history of previous exposure to a single high dose of SM gas during war. The control group was randomly selected from adjacent neighbors of the patients, and two healthy male subjects were chosen per patient. In this study, we used the validated Persian translation of Mayo Gastroesophageal Reflux Questionnaire to assess the frequency distribution of reflux disease. Results: Relative frequency of GERD symptoms, was found to be significantly higher in the inhalation injury patients with an odds ratio of 8.30 (95% confidence interval [CI]: 4.73-14.55, and after adjustment for cigarette smoking, tea consumption, age, and body mass index, aspirin and chronic cough the odds ratio was found to be 4.41 (95% CI: 1.61-12.07. Conclusion: The most important finding of our study was the major GERD symptoms (heartburn and/or acid regurgitation once or more per week among the individuals with the past history of exposure to SM toxic gas is substantially higher (4.4-fold than normal populations.

  13. [Toxicological and medico-legal analyses of sudden deaths resulting from butane inhalation].

    Science.gov (United States)

    Nowicka, Joanna; Kulikowska, Joanna; Korczyńska, Małgorzata; Celiński, Rafał; Chowaniec, Czesław

    2011-01-01

    Butane is known to be a suffocating gas with narcotic activity, especially at high concentrations. Within the past five years, a few cases of sudden deaths in teenage boys who had inhaled butane, a component of gas for lighters, were investigated in the Forensic Medicine Department, Medical University of Silesia, Katowice. Analyses of biological materials secured at autopsies and evidence from places of deaths was carried out using GC/FID. Butane was found in blood, lung and brain samples of the deceased. Moreover, histopathological examinations were performed. Results of autopsies and additional analyses were appraised from the point of view of their significance and usefulness in giving medico-legal opinions on the cause of death.

  14. Volatile fluorinated nanoemulsions: a chemical route to controlled delivery of inhalation anesthesia.

    Science.gov (United States)

    Salama, Ibrahim E; Jenkins, Claire L; Davies, Alun; Clark, Jeffrey N; Wilkes, Antony R; Hall, Judith E; Paul, Alison

    2015-02-15

    Novel dispersions of the volatile inhalation anesthetic sevoflurane have been formulated that can provide controlled, sustainable release of anesthetic over clinically useful timescales. The emulsions can be simply formed with manual shaking, reproducibly yielding droplets of the order of 250 nm diameter, i.e. within the nanoemulsion range. Using a custom flow-rig, release of anesthetic gas from the emulsion has been evaluated, and clinically useful levels achieved through appropriate stirring of the formulation. Stirring can also be used to temporarily increase or decrease the amount of anesthetic released. Once consideration of the unusual nature of the fluorinated systems (phase separation by sedimentation rather than creaming), and the highly perturbed environment of their evaluation (under stirring and flow of gas), the observed behavior regarding sevoflurane evaporation can be reasonably well explained by existing theoretical models. Links between anesthetic release and emulsion structure have been defined, providing the basis for future development. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Survivor from asphyxiation due to helium inhalation

    Directory of Open Access Journals (Sweden)

    Massimiliano Etteri

    2016-06-01

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

  16. Asthma and Adherence to Inhaled Corticosteroids

    DEFF Research Database (Denmark)

    Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli

    2015-01-01

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

  17. Occupational asthma induced by inhaled egg lysozyme.

    Science.gov (United States)

    Bernstein, J A; Kraut, A; Bernstein, D I; Warrington, R; Bolin, T; Warren, C P; Bernstein, I L

    1993-02-01

    A 26-year-old man employed in a company which manufactured hen egg white derived lysozyme for use in the pharmaceutical industry was evaluated for occupational asthma. The worker began to experience immediate-onset asthmatic symptoms two months after starting to work with egg lysozyme powder. The work process involved the production of approximately 1,000 kg of purified dried lysozyme powder per week. Prick skin testing was positive to egg lysozyme (50 mg/ml) and other egg protein components, but negative to whole egg white and egg yolk reagents. Serum specific IgE to egg lysozyme was documented. Decrements in serial peak expiratory flow rates were associated with lysozyme exposure at work. A specific bronchoprovocation challenge to lysozyme powder was positive demonstrating an isolated immediate asthmatic response (48 percent decrease from baseline FEV1). This is the first reported case of lysozyme-induced asthma specifically caused by inhalational exposure to egg lysozyme.

  18. Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.

    Science.gov (United States)

    Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kloft, Charlotte

    2015-07-01

    During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes, has strongly increased. However, this increase could not equally be observed for orally inhaled drugs. The objectives of this review are to understand the reasons for this gap and to demonstrate the opportunities that mathematical modeling of pharmacokinetics of orally inhaled drugs offers. To achieve these objectives, this review (i) discusses pulmonary physiological processes and their impact on the pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of published pharmacokinetic models, (iii) categorizes these models into physiologically based pharmacokinetic (PBPK) and (clinical data-derived) empirical models, (iv) explores both their (mechanistic) plausibility, and (v) addresses critical aspects of different pharmacometric approaches pertinent for drug inhalation. In summary, pulmonary deposition, dissolution, and absorption are highly complex processes and may represent the major challenge for modeling and simulation of PK after oral drug inhalation. Challenges in relating systemic pharmacokinetics with pulmonary efficacy may be another factor contributing to the limited number of existing pharmacokinetic models for orally inhaled drugs. Investigations comprising in vitro experiments, clinical studies, and more sophisticated mathematical approaches are considered to be necessary for elucidating these highly complex pulmonary processes. With this additional knowledge, the PBPK approach might gain additional attractiveness. Currently, (semi-)mechanistic modeling offers an alternative to generate and investigate hypotheses and to more mechanistically understand the pulmonary and systemic pharmacokinetics after oral drug inhalation including the impact of pulmonary diseases.

  19. In vivo

    Science.gov (United States)

    Freudenblum, Julia; Iglesias, José A; Hermann, Martin; Walsen, Tanja; Wilfinger, Armin; Meyer, Dirk; Kimmel, Robin A

    2018-02-08

    The three-dimensional architecture of the pancreatic islet is integral to beta cell function, but the process of islet formation remains poorly understood due to the difficulties of imaging internal organs with cellular resolution. Within transparent zebrafish larvae, the developing pancreas is relatively superficial and thus amenable to live imaging approaches. We performed in vivo time-lapse and longitudinal imaging studies to follow islet development, visualizing both naturally occurring islet cells and cells arising with an accelerated timecourse following an induction approach. These studies revealed previously unappreciated fine dynamic protrusions projecting between neighboring and distant endocrine cells. Using pharmacological compound and toxin interference approaches, and single-cell analysis of morphology and cell dynamics, we determined that endocrine cell motility is regulated by phosphoinositide 3-kinase (PI3K) and G-protein-coupled receptor (GPCR) signaling. Linking cell dynamics to islet formation, perturbation of protrusion formation disrupted endocrine cell coalescence, and correlated with decreased islet cell differentiation. These studies identified novel cell behaviors contributing to islet morphogenesis, and suggest a model in which dynamic exploratory filopodia establish cell-cell contacts that subsequently promote cell clustering. © 2018. Published by The Company of Biologists Ltd.

  20. In Vivo

    Science.gov (United States)

    Lau, Melissa; Li, Jianli; Cline, Hollis T

    2017-01-01

    The neurovascular niche is a specialized microenvironment formed by the interactions between neural progenitor cells (NPCs) and the vasculature. While it is thought to regulate adult neurogenesis by signaling through vascular-derived soluble cues or contacted-mediated cues, less is known about the neurovascular niche during development. In Xenopus laevis tadpole brain, NPCs line the ventricle and extend radial processes tipped with endfeet to the vascularized pial surface. Using in vivo labeling and time-lapse imaging in tadpoles, we find that intracardial injection of fluorescent tracers rapidly labels Sox2/3-expressing NPCs and that vascular-circulating molecules are endocytosed by NPC endfeet. Confocal imaging indicates that about half of the endfeet appear to appose the vasculature, and time-lapse analysis of NPC proliferation and endfeet-vascular interactions suggest that proliferative activity does not correlate with stable vascular apposition. Together, these findings characterize the neurovascular niche in the developing brain and suggest that, while signaling to NPCs may occur through vascular-derived soluble cues, stable contact between NPC endfeet and the vasculature is not required for developmental neurogenesis.

  1. IN VIVO

    Science.gov (United States)

    Jamila, Nargis; Khan, Naeem; Khan, Amir Atlas; Khan, Imran; Khan, Sadiq Noor; Zakaria, Zainal Amiruddin; Khairuddean, Melati; Osman, Hasnah; Kim, Kyong Su

    2017-01-01

    Garcinia hombroniana , known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract. In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl 4 )/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl 4 . Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1 H, 13 C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract. In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (pIR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents. From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

  2. [Severe burns related to steam inhalation therapy].

    Science.gov (United States)

    Belmonte, J A; Domínguez-Sampedro, P; Pérez, E; Suelves, J M; Collado, J M

    2015-02-01

    Despite lack of proven effectiveness and its potential to cause severe burns, steam inhalation therapy (SIT) is still used as a treatment for benign respiratory conditions. To characterize cases of burns related to steam inhalation therapy (BRSIT) in order to formulate appropriate preventive criteria. A review was conducted on cases of BRSIT admitted to a Burns Unit between 2006 and 2012, analysing epidemiological data, clinical aspects, severity and course. A total of 530 patients were admitted; 375 (70%) with scalds, and 15 with BRSIT (2.8% of burns; 4% of scalds). SIT was indicated in most cases for mild upper airway infections. The median age of patients was 7 years (2.5m-14 y). The burned area (BA) was ≥10% in 60% of cases (max. BA 22%). Injuries involved trunk, genital area, and extremities; only in one case was the face affected. The mean hospital length-of-stay was 14 days (3-30 d). Five patients (33%) were admitted to the PICU, most of them (60%) younger than 3 years. Eight patients (53%) underwent surgical treatment (skin grafting). In a 12-year-old patient whooping cough was diagnosed in the Burns Unit, and a 2.5-year-old patient developed staphylococcal toxic shock syndrome. No patient died. The final course was satisfactory in all patients. BRSIT can be severe and cause significant use of health resources. Professionals caring for children, particularly paediatricians, should seriously consider their prevention, avoiding treatments with SIT, and educating parents in order not to use it on their own. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  3. Producing nitric oxide by pulsed electrical discharge in air for portable inhalation therapy.

    Science.gov (United States)

    Yu, Binglan; Muenster, Stefan; Blaesi, Aron H; Bloch, Donald B; Zapol, Warren M

    2015-07-01

    Inhalation of nitric oxide (NO) produces selective pulmonary vasodilation and is an effective therapy for treating pulmonary hypertension in adults and children. In the United States, the average cost of 5 days of inhaled NO for persistent pulmonary hypertension of the newborn is about $14,000. NO therapy involves gas cylinders and distribution, a complex delivery device, gas monitoring and calibration equipment, and a trained respiratory therapy staff. The objective of this study was to develop a lightweight, portable device to serve as a simple and economical method of producing pure NO from air for bedside or portable use. Two NO generators were designed and tested: an offline NO generator and an inline NO generator placed directly within the inspiratory line. Both generators use pulsed electrical discharges to produce therapeutic range NO (5 to 80 parts per million) at gas flow rates of 0.5 to 5 liters/min. NO was produced from air, as well as gas mixtures containing up to 90% O2 and 10% N2. Potentially toxic gases produced in the plasma, including nitrogen dioxide (NO2) and ozone (O3), were removed using a calcium hydroxide scavenger. An iridium spark electrode produced the lowest ratio of NO2/NO. In lambs with acute pulmonary hypertension, breathing electrically generated NO produced pulmonary vasodilation and reduced pulmonary arterial pressure and pulmonary vascular resistance index. In conclusion, electrical plasma NO generation produces therapeutic levels of NO from air. After scavenging to remove NO2 and O3 and filtration to remove particles, electrically produced NO can provide safe and effective treatment of pulmonary hypertension. Copyright © 2015, American Association for the Advancement of Science.

  4. Increased steady-state VO2 and larger O2 deficit with CO2 inhalation during exercise

    DEFF Research Database (Denmark)

    Østergaard, Lars; Kjær, Kirsten; Jensen, Kurt

    2012-01-01

    Abstract Aim:  To examine whether inhalation of CO2-enriched gas would increase steady-state during exercise and enlarge O2 deficit. Methods:  Ten physically active men ( 53.7 ± 3.6 mL min−1 kg−1; ± SD) performed transitions from low-load cycling (baseline; 40 W) to work rates representing light...... (≈ 45%; 122 ± 15 W) and heavy (≈ 80%; 253 ± 29 W) exercise while inhaling normal air (air) or a CO2 mixture (4.2% CO2, 21% O2, balance N2). Gas exchange was measured with Douglas bag technique at baseline and at min 0–2, 2–3 and 5–6. Results:  Inhalation of CO2-enriched air consistently induced...... towards increased lipid oxidation (decline in R 0.12; P 2 min of exercise were not significantly different whereas the increase in from min 2–3 to min 5–6 in heavy exercise was larger with CO2 than with air suggesting a greater slow component. As a result, O2 deficit was greater...

  5. Age of Inhalant First Time Use and Its Association to the Use of Other Drugs

    Science.gov (United States)

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

    2009-01-01

    Inhalants are the 4th most commonly abused drugs after alcohol, tobacco, and marijuana. Although inhalants are often referred as Gateway Drugs this hypothesis is less examined. Using the 2003 National Survey on Drug Use and Health data, age of first time inhalant use was compared with the age of onset of other drugs among 6466 inhalant users who…

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

    NARCIS (Netherlands)

    Gigengack, R.A.

    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

  7. The chemo and the mona : Inhalants, devotion and street youth in Mexico city

    NARCIS (Netherlands)

    Gigengack, Roy

    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

  8. Retail sales of inhalation devices in European countries: so much for a global policy

    DEFF Research Database (Denmark)

    Lavorini, F; Corrigan, C J; Barnes, P J

    2011-01-01

    To evaluate the retail sales of pressurised metered-dose inhalers (pMDIs), dry-powder inhalers (DPIs) and liquids for nebulisation in 16 European countries.......To evaluate the retail sales of pressurised metered-dose inhalers (pMDIs), dry-powder inhalers (DPIs) and liquids for nebulisation in 16 European countries....

  9. Urine and serum concentrations of inhaled and oral terbutaline

    DEFF Research Database (Denmark)

    Elers, Jimmi; Hostrup, Morten; Pedersen, Lars

    2012-01-01

    We examined urine and serum concentrations after therapeutic use of single and repetitive doses of inhaled and supratherapeutic oral use of terbutaline. We compared the concentrations in 10 asthmatics and 10 healthy subjects in an open-label, cross-over study with 2 mg inhaled and 10 mg oral...... differences in urine and serum concentrations between asthmatic and healthy subjects. We compared urine and serum concentrations after therapeutic inhaled doses and supratherapeutic oral doses and observed significant statistical differences in both groups but found it impossible to distinguish between...... therapeutic and prohibited use based on doping tests with urine and blood samples....

  10. Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

    OpenAIRE

    Kale, Ashutosh; Shackley, Fiona

    2010-01-01

    We report a case of accidental cutaneous burns caused by salbutamol metered dose inhaler. A 9-year-old boy underwent dental extraction at a children's hospital and was incidentally noted to have burn injuries on dorsum of both hands. On questioning, the boy revealed that a few days ago his 14-year-old brother, who is an asthmatic, playfully sprayed his salbutamol metered dose inhaler on the back of both his hands with the inhaler's mouth piece being in direct contact with the patient's skin. ...

  11. Inhalation carcinogenicity of dichloromethane in rats and mice.

    Science.gov (United States)

    Aiso, Shigetoshi; Take, Makoto; Kasai, Tatsuya; Senoh, Hideki; Umeda, Yumi; Matsumoto, Michiharu; Fukushima, Shoji

    2014-07-01

    The carcinogenicity of inhaled dichloromethane (DCM) was examined by exposing groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of both sexes to 0, 1000, 2000, or 4000 ppm (w/w) DCM-containing aerosol for 2 years. Inhalation of DCM resulted in increased incidences of subcutis fibromas, mammary gland fibroadenoma, and peritoneum mesotheliomas in male rats; mammary gland fibroadenomas in female rats; and bronchiolar-alveolar adenomas and carcinomas in the lung and hepatocellular adenomas and carcinomas in male and female mice. These results clearly indicate that inhaled DCM is carcinogenic in F344/DuCrj (SPF) rats and Crj: BDF1 (SPF) mice.

  12. Comparative Metabolism of Carbon Tetrachloride in Rats, Mice and Hamsters Using Gas Uptake and PBPK Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Thrall, Karla D.(BATTELLE (PACIFIC NW LAB)); Vucelick, Mark E.(FLUOR HANFORD, INC); Gies, Richard A.(BATTELLE (PACIFIC NW LAB)); Zangar, Richard C.(BATTELLE (PACIFIC NW LAB)); Weitz, Karl K.(BATTELLE (PACIFIC NW LAB)); Poet, Torka S.(BATTELLE (PACIFIC NW LAB)); Springer, David L.(BATTELLE (PACIFIC NW LAB)); Grant, Donna M.(BATTELLE (PACIFIC NW LAB)); Benson, Janet M.(Inhalation Toxicology Research Institute)

    2000-08-25

    No study has comprehensively compared the rate of metabolism of carbon tetrachloride (CCl4) across species. Therefore, the in vivo metabolism of CCl4 was evaluated using groups of male animals (F344 rats, B6C3F1 mice, and Syrian hamsters) exposed to 40-1800 ppm CCl4 in a closed, recirculating gas-uptake system. For each species, an optimal fit of the family of uptake curves was obtained by adjusting Michaelis-Menten metabolic constants Km (affinity) and Vmax (capacity) using a physiologically based pharmacokinetic (PBPK) model. The results show that the mouse has a slightly higher capacity and lower affinity for metabolizing CCl4 compared to the rat, while the hamster has a higher capacity and lower affinity than either rat or mouse. A comparison of the Vmax to Km ratio, normalized for mg of liver protein (L/hr/mg) across species indicates that hamsters metabolize more CCl4 than either rats or mice, and should be more susceptible to CCl4-induced hepatotoxicity. These species comparisons were evaluated against toxicokinetic studies conducted in animals exposed by nose-only inhalation to 20 ppm 14C-labeled CCl4 for 4 hours. The toxicokinetic study results are consistent with the in vivo rates of metabolism, with rats eliminating less radioactivity associated with metabolism (14CO2 and urine/feces) and more radioactivity associated with the parent compound (radioactivity trapped on charcoal) compared to either hamsters or mice. The in vivo metabolic constants determined here, together with in vitro constants determined using rat, mouse, hamster and human liver microsomes, were used to estimate human in vivo metabolic rates of 1.49 mg/hr/kg body weight and 0.25 mg/L for Vmax and Km, respectively. Normalizing the rate of metabolism (Vmax/Km) by mg liver protein, the rate of metabolism of CCl4 differs across species, with hamster > mouse& > rat > human.

  13. Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model

    Directory of Open Access Journals (Sweden)

    O'Shaughnessy Patrick T

    2011-01-01

    Full Text Available Abstract Background There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure. Results In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m3, 4 hours/day, 10 days, 5 ± 2 nm primary size. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma - optical emission spectroscopy (ICP-OES was 31 μg/g lung (dry weight immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu. Conclusions Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

  14. Microbiological community in biogas systems and evaluation of microbial risks from gas usage

    Energy Technology Data Exchange (ETDEWEB)

    Vinneraas, B.; Nordin, A. [Swedish Univ. of Agricultural Sciences, Dept. of Biometry and Engineering, Uppsala (Sweden); Schoenning, C. [Swedish Inst. for Infectious Disease Control, Dept. of Parasitology, Mycology, Environmental Mirobiology and Water, Solna (Sweden)

    2007-12-15

    The plans for introducing biogas produced from organic waste to the pipe system for natural gas have raised concerns about the risk of transmitting disease via the gas. To assess this risk, condensate water from gas pipes and gas from different parts of biogas upgrading systems were sampled and cultured for microbial content. The number of microorganisms found in the biogas correspond to the densities in sampled natural gas. Since no pathogens were identified and since the exposure to gas from e. g. cookers and refueling of cars may only result in the inhalation of small volumes of gas, the risk of spreading disease via biogas was judged to be very low. (orig.)

  15. Effect of maximum inhalation flow and inhaled volume on formoterol drug deposition in-vitro from an Easyhaler® dry powder inhaler.

    Science.gov (United States)

    Abadelah, Mohamad; Hazim, Firisteh; Chrystyn, Henry; Bagherisadeghi, Golshan; Rahmoune, Hassan; Larhrib, Hassan

    2017-06-15

    Most patients using dry powder inhalers (DPIs) do not achieve the inhalation parameters recommended for pharmacopoeial in-vitro dose emission testing. The dose emission characteristics of formoterol from an Easyhaler® have been measured using the Andersen Cascade Impactor (ACI) with a maximum inhalation flow (MIF) of 28.3, 60 and 90L/min and inhaled volumes (Vin) of 240, 750, 1500 and 2000mL. The total emitted dose (TED) was significantly higher at 90L/min (pMMAD) was smaller at 90L/min across all Vin values. Dose emission characteristics were lower at 240mL for both MIFs. The results for 240mL could be due to an insufficient Vin pulled through the ACI or incomplete emptying of the dose metering cup. This study shows that the FPD, %FPF and MMAD were not significantly affected by the vin≥750mL and that an inhaled volume as low as 750mL could be used with the ACI. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Finney, Lydia; Berry, Matthew; Singanayagam, Aran; Elkin, Sarah L; Johnston, Sebastian L; Mallia, Patrick

    2014-11-01

    Inhaled corticosteroids are widely used in chronic obstructive pulmonary disease (COPD) and, in combination with long-acting β2 agonists, reduce exacerbations and improve lung function and quality of life. However, inhaled corticosteroids have been linked with an increased risk of pneumonia in individuals with COPD, but the magnitude of this risk, the effects of different preparations and doses, and the mechanisms of this effect remain unclear. Therefore, making informed clinical decisions--balancing the beneficial and adverse effects of inhaled corticosteroids in individuals with COPD--is difficult. Understanding of the mechanisms of increased pneumonia risk with inhaled corticosteroids is urgently needed to clarify their role in the management of COPD and to aid the development of new, safer therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Fiber inhalability and head deposition in rats and humans.

    Science.gov (United States)

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

  18. Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers : a systematic review

    NARCIS (Netherlands)

    Farzan, N.|info:eu-repo/dai/nl/412501929; Vijverberg, S.J.H.|info:eu-repo/dai/nl/325847460; Arets, H.G.M.; Raaijmakers, J.A.M.|info:eu-repo/dai/nl/072763299; van der Zee, A.H.|info:eu-repo/dai/nl/255164688

    BACKGROUND Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited. OBJECTIVE To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and

  19. [Inhaled treatments in cystic fibrosis: what's new in 2013?].

    Science.gov (United States)

    Dubus, J-C; Bassinet, L; Chedevergne, F; Delaisi, B; Desmazes-Dufeu, N; Reychler, G; Vecellio, L

    2014-04-01

    In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  20. Hypertrichosis as a side effect of inhaled steroids in children

    NARCIS (Netherlands)

    de Vries, T. W.; de Langen-Wouterse, J. J.; de Jong-van den Berg, L. T. W.; Duiverman, E. J.

    Three spontaneous reports of patients in whom a relationship between hypertrichosis and inhaled corticosteroids (ICS) was suspected, were reported to Lareb, The Netherlands Pharmacovigilance Center. We sought evidence for and against a causal relationship between hypertrichosis and ICS in children.

  1. Carbon monoxide inhalation induces headache in a human headache model

    DEFF Research Database (Denmark)

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

    2017-01-01

    Introduction Carbon monoxide (CO) is an endogenously produced signalling molecule that has a role in nociceptive processing and cerebral vasodilatation. We hypothesized that inhalation of CO would induce headache and vasodilation of cephalic and extracephalic arteries. Methods In a randomized...

  2. Development of an intelligent adapter for metered dose inhalers

    Directory of Open Access Journals (Sweden)

    Zhang Mingrong

    2016-01-01

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

  3. Interactions between diltiazem and inhalation anaesthetics in the isolated heart.

    Science.gov (United States)

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

    1989-09-01

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

  4. Gas transport duringin vitroandin vivopreclinical testing of inert gas therapies.

    Science.gov (United States)

    Katz, Ira; Palgen, Marc; Murdock, Jacqueline; Martin, Andrew R; Farjot, Géraldine; Caillibotte, Georges

    2016-03-01

    New gas therapies using inert gases such as xenon and argon are being studied, which require in vitro and in vivo preclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze an in vitro experiment for gas transport to a 96 cell well plate and an in vivo delivery to a small animal chamber, where the key processes considered are the wash-in of test gas into an apparatus dead volume, the diffusion of test gas through the liquid media in a well of a cell test plate, and the pharmacokinetics in a rat. In the case of small animals in a chamber, the key variable controlling the kinetics is the chamber wash-in time constant that is a function of the chamber volume and the gas flow rate. For cells covered by a liquid media the diffusion of gas through the liquid media is the dominant mechanism, such that liquid depth and the gas diffusion constant are the key parameters. The key message from these analyses is that the transport of gas during preclinical experiments can be important in determining the true dose as experienced at the site of action in an animal or to a cell.

  5. Effect of clay nanoparticles on model lung surfactant: a potential marker of hazard from nanoaerosol inhalation.

    Science.gov (United States)

    Kondej, Dorota; Sosnowski, Tomasz R

    2016-03-01

    This work investigates influence of different aluminosillicate nanoparticles (NPs) which are found in air in selected workplaces on the properties of the phospholipid (DPPC) monolayer at air-saline interface considered as ex vivo model of the lung surfactant (LS). The measurements were done under physiological-like conditions (deformable liquid interface at 37 °C) for NP concentrations matching the calculated lung doses after exposure in the working environment. Measured surface pressure-area (π-A) isotherms and compressibility curves demonstrated NP-induced changes in the structure and mechanical properties of the lipid monolayer. It was shown that hydrophilic nanomaterials (halloysite and bentonite) induced concentration-dependent impairment of DPPC's ability of attaining high surface pressures on interfacial compression, suggesting a possibility of reduction of physiological function of natural LS. Hydrophobic montmorillonites affected DPPC monolayer in the opposite way; however, they significantly changed the mechanical properties of the air-liquid interface during compression. The results support the hypothesis of possible reduction or even degradation of the natural function of the lung surfactant induced by particle-phospholipid interactions after inhalation of nanoclays. Presented data do not only supplement the earlier results obtained with another LS model (animal-derived surfactant in oscillating bubble experiments) but also offer an explanation of physicochemical mechanisms responsible for detrimental effects which arise after deposition of inhaled nanomaterials on the surface of the respiratory system.

  6. Aerodynamics and deposition effects of inhaled submicron drug aerosol in airway diseases.

    Science.gov (United States)

    Faiyazuddin, Md; Mujahid, Md; Hussain, Talib; Siddiqui, Hefazat H; Bhatnagar, Aseem; Khar, Roop K; Ahmad, Farhan J

    2013-01-01

    Particle engineering is the prime focus to improve pulmonary drug targeting with the splendor of nanomedicines. In recent years, submicron particles have emerged as prettyful candidate for improved fludisation and deposition. For effective deposition, the particle size must be in the range of 0.5-5 μm. Inhalers design for the purpose of efficient delivery of powders to lungs is again a crucial task for pulmonary scientists. A huge number of DPI devices exist in the market, a significant number are awaiting FDA approval, some are under development and a large number have been patented or applied for patent. Even with superior design, the delivery competence is still deprived, mostly due to fluidisation problems which cause poor aerosol generation and deposition. Because of the cohesive nature and poor flow characteristics, they are difficult to redisperse upon aerosolization with breath. These problems are illustrious in aerosol research, much of which is vastly pertinent to pulmonary therapeutics. A technical review is presented here of advances that have been utilized in production of submicron drug particles, their in vitro/in vivo evaluations, aerosol effects and pulmonary fate of inhaled submicron powders.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-06-01

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

  8. Effectiveness of activated carbon masks in preventing anticancer drug inhalation

    OpenAIRE

    Sato, Junya; Kogure, Atushi; Kudo, Kenzo

    2016-01-01

    Background The exposure of healthcare workers to anticancer drugs such as cyclophosphamide (CPA) is a serious health concern. Anticancer drug pollution may spread outside biological safety cabinets even when a closed system is used. The inhalation of vaporized anticancer drugs is thought to be the primary route of exposure. Therefore, it is important that healthcare workers wear masks to prevent inhalation of anticancer drugs. However, the permeability of medical masks to vaporized anticancer...

  9. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  10. Radioaerosol Inhalation Imaging in Bronchial Asthma

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-15

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

  11. Penthrox inhaler analgesia in transrectal ultrasound-guided prostate biopsy.

    Science.gov (United States)

    Lee, Chanyang; Woo, Henry H

    2015-06-01

    Periprostatic injection of local anaesthetic (PILA) has been shown to significantly reduce pain in patients undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB). However, this method does not address pain that is associated with ultrasound probe insertion, and the injection of local anaesthetic itself causes pain. The aim of this study was to explore the efficacy of methoxyflurane delivered by a Penthrox inhaler as a novel method of pain relief during TRUSPB. From July 2012 to July 2013, 64 patients were scheduled at a single centre to undergo TRUSPB while receiving analgesia via Penthrox inhaler. Fifteen minutes after the biopsy procedure, these patients were asked to complete a pain score survey using a 10-cm visual analogue scale (VAS) to separately report the degree of pain experienced during digital rectal examination (DRE), ultrasound probe insertion and core biopsy. The median pain scores on a 10-cm VAS were 2.0, 2.4 and 3.0 during DRE, probe insertion and needle biopsy, respectively, while using the Penthrox inhaler. Of the 64 patients, 11 had undergone TRUSPB previously receiving PILA. In these patients, PILA was significantly better than the Penthrox inhaler for pain relief during needle biopsy (median pain score 2.0 versus 4.0; P = 0.012). The Penthrox inhaler appears to be a safe and effective method of analgesia for TRUSPB. Patients who had experienced both PILA and Penthrox reported pain scores that significantly favoured PILA over the Penthrox inhaler. © 2014 Royal Australasian College of Surgeons.

  12. Steam inhalation therapy: severe scalds as an adverse side effect

    Science.gov (United States)

    Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne

    2012-01-01

    Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

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

    Science.gov (United States)

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

    2013-11-30

    The study aims to investigate the impact of various design parameters of a dry powder inhaler on the turbulence intensities generated and the performance of the dry powder inhaler. The flow fields and turbulence intensities in the dry powder inhaler are measured using particle image velocimetry (PIV) techniques. In vitro aerosolization and deposition a blend of budesonide and lactose are measured using an Andersen Cascade Impactor. Design parameters such as inhaler grid hole diameter, grid voidage and chamber length are considered. The experimental results reveal that the hole diameter on the grid has negligible impact on the turbulence intensity generated in the chamber. On the other hand, hole diameters smaller than a critical size can lead to performance degradation due to excessive particle-grid collisions. An increase in grid voidage can improve the inhaler performance but the effect diminishes at high grid voidage. An increase in the chamber length can enhance the turbulence intensity generated but also increases the powder adhesion on the inhaler wall. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Quantifying and reducing inhaler prescription errors in secondary care.

    Science.gov (United States)

    Zaidi, Seher; Mordaunt, Cathy; Durnin, Nicola; Cooke, Sarah; Blakey, John D

    2015-12-01

    Junior doctors commonly prescribe inhaled medication for patients admitted to hospitals, and this may be a potential source of prescription error. Objective To determine the potential type, frequency and cost of prescription errors for inhaled medication, and ascertain if a simple educational intervention can improve junior doctors' knowledge and reduce these. We carried out a prospective study looking at the types and cost of inhaled prescription errors. Simultaneously we tested knowledge of junior doctors' using a quiz. Both the studies were carried out before and after the introduction of inhaler flash cards (pictures of devices with, instructions on use and the medication they contain) on specific wards. This was followed by an electronic feedback survey. Error rates varied greatly (p = 6.8 × 10(-8)) by device, with 23 % of Evohaler and Accuhaler prescriptions being incorrect. The average cost of an erroneously prescribed medication was £45.50. There were 14 % incorrect prescriptions before the intervention. There was no significant improvement in junior doctors' knowledge of inhalers or the rate of prescription error after the intervention. Prescription errors of inhaled medication are common and costly to rectify. There is a need for improved teaching and training of junior doctors and medical students.

  15. A dry powder inhaler with reduced mouth-throat deposition.

    Science.gov (United States)

    Wang, Z L; Grgic, B; Finlay, W H

    2006-01-01

    A novel, compact, and highly efficient dry powder inhaler (DPI) with low mouth-throat deposition is described. The performance of this DPI was evaluated by measuring both (1) the total aerosol deposition in and distal to an idealized mouth-throat cast and (2) the fine particle fraction (FPF) using a standard Mark II Anderson impactor. Ultraviolet (UV) spectroscopy techniques were used in the aerosol deposition measurements. Two inhalation aerosol powders, namely budesonide (extracted from a Pulmicort/Turbuhaler multi-dose device, 200 microg/dose) and ciprofloxacin + lipid + lactose (in-house), were dispersed by the DPI at a steady inhalation flow rate of 60 L/min. The newly developed DPI had a total aerosol delivery distal to the mouth-throat cast of 50.5% +/- 3.04% and 69.7% +/- 1.5% for the budesonide and ciprofloxacin + lipid + lactose aerosols, respectively. This is a significant improvement over the Turbuhaler original device delivery of 34.5% +/- 5.2%, particularly considering that in vitro mouth-throat deposition dropped from 27.5% +/- 5.4% with the budesonide Turbuhaler to 11.0% +/- 3.5% with the present inhaler. The different lung deliveries from the same inhaler for the two formulations above also confirm that the overall performance of an inhaler is optimizable via powder formulations.

  16. Stereoselectivity of the TDxADx/FLx Amphetamine/Methamphetamine II amphetamine/methamphetamine immunoassay--response of urine specimens following nasal inhaler use.

    Science.gov (United States)

    Poklis, A; Moore, K A

    1995-01-01

    The TDxADx/FLx Amphetamine/Methamphetamine II fluorescence polarization immunoassay (Abbott Diagnostic) for the detection of amphetamine and methamphetamine in urine was evaluated for stereoselectivity and response to specimens collected following as recommended and double the recommended dose use of Vicks Nasal Inhaler. The assay is calibrated with d-amphetamine, at cutoff concentration of 300 ng/mL for a positive response. Cross-reactivity studies demonstrated a positive result with 1000 ng/mL l-amphetamine, 300 ng/mL d-methamphetamine, and approximately 2000 ng/mL desoxyephedrine. A good correlation was observed between urines obtained following ingestion of d-amphetamine simultaneously analyzed by TDxADx/FLx Amphetamine/Methamphetamine II and gas chromatography/mass spectrometry: r2 = 0.954, N = 100. However, urine obtained following ingestion of racemic methamphetamine showed no correlation between TDxADx/FLx Amphetamine/Methamphetamine II and gas chromatography/mass spectrometry results: r2 = 0.420, N = 28. Urines collected following as recommended use for five consecutive days of Vicks Nasal Inhaler containing l-desoxyephedrine did not yield positive TDxADx/FLx Amphetamine/Methamphetamine II results. Only two urines from a subject using twice the recommended inhaler dose yielded positive TDxADx/FLx Amphetamine/Methamphetamine II results. These urines contained 1560 and 1530 ng/mL desoxyephedrine when analyzed by gas chromatography/mass spectrometry. Greater than recommended use of Vicks Nasal Inhaler may yield false positive TDxADx/FLx Amphetamine/Methamphetamine II results for amphetamine use when calibrated at 300 ng/mL d-amphetamine. If calibrated at 1000 ng/mL, d-amphetamine, the TDxADx/FLx Amphetamine/Methamphetamine II is unlikely to yield false positive results for amphetamine, even following excessive inhaler use.

  17. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies.

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

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

    2015-08-30

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

  19. Electrostatics and inhaled medications: influence on delivery via pressurized metered-dose inhalers and add-on devices

    National Research Council Canada - National Science Library

    Mitchell, Jolyon P; Coppolo, Dominic P; Nagel, Mark W

    2007-01-01

    .... Spacers and valved holding chambers used with pressurized metered-dose inhalers to treat obstructive lung diseases are particularly prone to this behavior, which increases variability in the amount...

  20. An in vitro Method for Predicting Inhalation Toxicity of Impregnation Spray Products

    DEFF Research Database (Denmark)

    Sørli, Jorid B.; Hansen, Jitka S.; Nørgaard, Asger Wisti

    2015-01-01

    Impregnation spray products are used for making surfaces water and dirt repellent. The products are composed of one or more active film-forming components dissolved or suspended in an appropriate solvent mixture. Exposure to impregnation spray products may cause respiratory distress and new cases...... of the inhalation toxicity of impregnation spray products and thus may reduce the need for animal testing....... of this study was to evaluate whether disruption of the pulmonary surfactant film can be used as a predictor of the toxic effects in vivo. Nine impregnation products with various chemical compositions were selected for testing and the main constituents of each product, e.g., solvents, co-solvents and film...... and in vivo. The true positive rate of the in vitro method was 100%, i.e. the test could correctly identify all products with toxic effects in vivo, the true negative rate was 40%. Investigation of inhibition of the pulmonary surfactant system, e.g. by capillary surfactometry, was found useful for evaluation...

  1. De-agglomeration Effect of the US Pharmacopeia and Alberta Throats on Carrier-Based Powders in Commercial Inhalation Products.

    Science.gov (United States)

    Leung, Sharon Shui Yee; Tang, Patricia; Zhou, Qi Tony; Tong, Zhenbo; Leung, Cassandra; Decharaksa, Janwit; Yang, Runyu; Chan, Hak-Kim

    2015-11-01

    The US pharmacopeia (USP) and Alberta throats were recently reported to cause further de-agglomeration of carrier-free powders emitted from some dry powder inhalers (DPIs). This study assessed if they have similar influences on commercially available carrier-based DPIs. A straight tube, a USP throat, and an Alberta throat (non-coated and coated) were used for cascade impaction testing. Aerosol fine particle fraction (FPF ≤ 5 μm) was computed to evaluate throat-induced de-agglomeration. Computational fluid dynamics are employed to simulate airflow patterns and particle trajectories inside the USP and Alberta throats. For all tested products, no significant differences in the in vitro aerosol performance were observed between the USP throat and the straight tube. Using fine lactose carriers (10 μm), impaction frequency and energy inside the Alberta throat were significant. Further de-agglomeration was noted inside the non-coated Alberta throat for Seretide(®) and Spiriva(®), but agglomerates emitted from Relenza(®), Ventolin(®), and Foradil(®) did not further break up into smaller fractions. The coated Alberta throat considerably reduced the FPF values of these products due to the high throat retention, but they generally agreed better with the in vivo data. In conclusion, depending on the powder formulation (including carrier particle size), the inhaler, and the induction port, further de-agglomeration could happen ex-inhaler and create differences in the in vitro measurements.

  2. Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS).

    Science.gov (United States)

    Leigh, Noel J; Lawton, Ralph I; Hershberger, Pamela A; Goniewicz, Maciej L

    2016-11-01

    E-cigarettes or electronic nicotine delivery systems (ENDS) are designed to deliver nicotine-containing aerosol via inhalation. Little is known about the health effects of flavoured ENDS aerosol when inhaled. Aerosol from ENDS was generated using a smoking machine. Various types of ENDS devices or a tank system prefilled with liquids of different flavours, nicotine carrier, variable nicotine concentrations and with modified battery output voltage were tested. A convenience sample of commercial fluids with flavour names of tobacco, piña colada, menthol, coffee and strawberry were used. Flavouring chemicals were identified using gas chromatography/mass spectrometry. H292 human bronchial epithelial cells were directly exposed to 55 puffs of freshly generated ENDS aerosol, tobacco smoke or air (controls) using an air-liquid interface system and the Health Canada intense smoking protocol. The following in vitro toxicological effects were assessed: (1) cell viability, (2) metabolic activity and (3) release of inflammatory mediators (cytokines). Exposure to ENDS aerosol resulted in decreased metabolic activity and cell viability and increased release of interleukin (IL)-1β, IL-6, IL-10, CXCL1, CXCL2 and CXCL10 compared to air controls. Cell viability and metabolic activity were more adversely affected by conventional cigarettes than most tested ENDS products. Product type, battery output voltage and flavours significantly affected toxicity of ENDS aerosol, with a strawberry-flavoured product being the most cytotoxic. Our data suggest that characteristics of ENDS products, including flavours, may induce inhalation toxicity. Therefore, ENDS users should use the products with caution until more comprehensive studies are performed. 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/.

  3. Combined anticoagulants ameliorate acute lung injury in sheep after burn and smoke inhalation.

    Science.gov (United States)

    Enkhbaatar, Perenlei; Esechie, Aimalohi; Wang, Jianpu; Cox, Robert A; Nakano, Yoshimitsu; Hamahata, Atsumori; Lange, Matthias; Traber, Lillian D; Prough, Donald S; Herndon, David N; Traber, Daniel L

    2008-02-01

    Burn and smoke inhalation-related multiple organ dysfunction is associated with a severe fall in the plasma concentration of antithrombin. Therefore the aim of the present study was to test the hypothesis that intravenous administration of recombinant human antithrombin in combination with aerosolized heparin will ameliorate acute lung injury in sheep exposed to cutaneous burn and smoke inhalation. Sheep were prepared operatively for study and, 7 days post-surgery, sheep were given a cutaneous burn (40% of total body surface area, third-degree burn) and insufflated with cotton smoke (48 breaths, injury, sheep were placed on a ventilator and resuscitated with Ringer's lactate solution. The animals were divided into three groups: sham group (non-injured and non-treated; n=6), saline group (injured and received saline; n=6) and rhAT.iv.+Hep group [injured and treated with rhAT (recombinant human antithrombin) and heparin; n=6]. In the rhAT.iv.+Hep group, rhAT was infused continuously for 48 h starting 1 h post-injury with a dose of 0.34 mg.h(-1).kg(-1) of body weight and heparin (10000 units) was aerosolized every 4 h starting at 1 h post-injury. The experiment lasted 48 h. Haemodynamics were stable in sham group, whereas the saline-treated sheep developed multiple signs of acute lung injury, including decreased pulmonary gas exchange, increased inspiratory pressures, extensive airway obstruction and increased pulmonary oedema. These pathological changes were associated with a severe fall in plasma antithrombin concentration, lung tissue accumulation of leucocytes and excessive production of NO. Treatment of injured sheep with anticoagulants attenuated all of the pulmonary pathophysiology observed. In conclusion, the results provide definitive evidence that anticoagulant therapy may be a novel and effective treatment tool in the management of burn patients with concomitant smoke inhalation injury.

  4. Cariogenic Potential of Inhaled Antiasthmatic Drugs.

    Science.gov (United States)

    Brigic, Amela; Kobaslija, Sedin; Zukanovic, Amila

    2015-08-01

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

  5. Health effects due to endotoxin inhalation (review)

    Energy Technology Data Exchange (ETDEWEB)

    Liebers, V.; Raulf-Heimsoth, M.; Bruening, T. [Ruhr-University Bochum, BGFA, Research Institute of Occupational Medicine, German Social Accident Insurance, Bochum (Germany)

    2008-04-15

    Endotoxins are ubiquitous in the environment and represent important components of bioaerosols. High exposure occurs in rural environment and at several workplaces (e.g. waste collecting, textile industry etc.). Adverse effects on human health induced by inhalation of endotoxin are described in several studies. Up to now the endotoxin levels are mainly measured using the Limulus amoebocyte-lysate (LAL) assay. This assay is well established, but for a suitable characterization of bioaerosols more parameters are necessary. Additional information, e.g. concerning the pyrogenic activity of organic dust samples may be delivered by whole blood assay. Whereas on the one hand protection measures at workplaces are demanded to avoid lung function impairment due to endotoxin exposure, on the other hand a protective effect of exposure to microbial agents like endotoxins with regard to allergy development has been observed. On the cellular level toll-like receptor 4 (TLR4) and IL-1 receptor as well as surface molecules like CD14 have been shown to play a pivotal role in the endotoxin activation cascade. In this review we summarize the mechanism of endotoxin recognition and its manifold effects on human health. (orig.)

  6. Inhalational Steroids and Iatrogenic Cushing's Syndrome.

    Science.gov (United States)

    A V, Raveendran

    2014-01-01

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

  7. Gas Sensor

    KAUST Repository

    Luebke, Ryan

    2015-01-22

    A gas sensor using a metal organic framework material can be fully integrated with related circuitry on a single substrate. In an on-chip application, the gas sensor can result in an area-efficient fully integrated gas sensor solution. In one aspect, a gas sensor can include a first gas sensing region including a first pair of electrodes, and a first gas sensitive material proximate to the first pair of electrodes, wherein the first gas sensitive material includes a first metal organic framework material.

  8. The prevalence and clinical significance of inhalant withdrawal symptoms among a national sample

    Directory of Open Access Journals (Sweden)

    Vaughn MG

    2011-04-01

    Full Text Available Brian E Perron1, Joseph E Glass2, Brian K Ahmedani3, Michael G Vaughn4, Daniel E Roberts1, Li-Tzy Wu51University of Michigan, Ann Arbor, MI, USA; 2Washington University, St Louis, MO, USA; 3Henry Ford Health System, Detroit, MI, USA; 4St Louis University, St Louis, MO, USA; 5Duke University, Durham, NC, USABackground: Inhalants are among the most common and dangerous forms of substance use, but very little research on inhalant use disorders exist. Unlike other substances, the Diagnostic and Statistical Manual, 4th edition (DSM-IV indicates that inhalants do not have an associated withdrawal syndrome among persons who meet criteria for inhalant dependence.Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions, this study examines the prevalence of withdrawal symptoms among inhalant users. Prevalence of inhalant withdrawal symptoms for inhalants was also compared with the prevalence of cocaine withdrawal symptoms to help determine the presence of an inhalant withdrawal syndrome.Results: Approximately 47.8% of persons who met criteria for inhalant dependence reported experiencing three or more inhalant-related withdrawal symptoms that were clinically significant. Among those with inhalant dependence, almost half of the withdrawal symptoms were as common as the corresponding withdrawal symptoms experienced by persons with cocaine dependence. Furthermore, the percentage of persons with inhalant dependence reporting clinically significant inhalant withdrawal symptoms was almost equal to the percentage of persons with cocaine dependence reporting clinically significant cocaine withdrawal symptoms.Conclusions: These data provide evidence for an inhalant-related withdrawal syndrome among persons with inhalant dependence. Revisions to DSM-IV should consider including inhalant withdrawal as a diagnostic criterion for this disorder.Keywords: Inhalants, volatile solvents, withdrawal, inhalant use disorders

  9. Long-term effects of aluminium dust inhalation.

    Science.gov (United States)

    Peters, Susan; Reid, Alison; Fritschi, Lin; de Klerk, Nicholas; Musk, A W Bill

    2013-12-01

    During the 1950s and 1960s, aluminium dust inhalation was used as a potential prophylaxis against silicosis in underground miners, including in Australia. We investigated the association between aluminium dust inhalation and cardiovascular, cerebrovascular and Alzheimer's diseases in a cohort of Australian male underground gold miners. We additionally looked at pneumoconiosis mortality to estimate the effect of the aluminium therapy. SMRs and 95% CI were calculated to compare mortality of the cohort members with that of the Western Australian male population (1961-2009). Internal comparisons on duration of aluminium dust inhalation were examined using Cox regression. Aluminium dust inhalation was reported for 647 out of 1894 underground gold miners. During 42 780 person-years of follow-up, 1577 deaths were observed. An indication of increased mortality of Alzheimer's disease among miners ever exposed to aluminium dust was found (SMR=1.38), although it was not statistically significant (95% CI 0.69 to 2.75). Rates for cardiovascular and cerebrovascular death were above population levels, but were similar for subjects with or without a history of aluminium dust inhalation. HRs suggested an increasing risk of cardiovascular disease with duration of aluminium dust inhalation (HR=1.02, 95% CI 1.00 to 1.04, per year of exposure). No difference in the association between duration of work underground and pneumoconiosis was observed between the groups with or without aluminium dust exposure. No protective effect against silicosis was observed from aluminium dust inhalation. Conversely, exposure to aluminium dust may possibly increase the risk of cardiovascular disease and dementia of the Alzheimer's type.

  10. Inhaled Surfactant Therapy in Newborns in Artificial Lung Ventilation

    Directory of Open Access Journals (Sweden)

    S. A. Perepelitsa

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency of inhaled surfactant therapy in neonatal infants with respiratory failure.Subjects and methods. The trial enrolled 13 premature neonatal infants; their mean gestational age was 31.8±2.8 weeks and the birth weight was 1825±600.9 g. They had a oneminute Apgar score of 4.3±1.4. All the neonates needed mechanical ventilation (MV atbirth because the leading clinical sign was respiratory failure caused by acute intranatal hypoxia, neonatal amniotic fluid aspiration, respiratory distress syndrome (RDS, and cerebral ischemia. Curosurf was injected in a dose of 174.7±21 mg/kg in the infants with neonatal RDS at 35 minutes of life. All the babies included in the study were noted to have severe disease and prolonged MV. After stabilization of their status, the neonates received combination therapy involving surfactantBL inhalation to reduce the duration of MV. The dose of the agent was 75 mg. Results. After surfactantBL inhalation, effective spontaneous respiration occurred in 69.2% of the newborn infants; successful extubation was carried out. The median duration ofMV after surfactant BL inhalation was 22 hours (4—68 hours. There were no reintubated cases after inhalation therapy. Following surfactantBL inhalation, 4 (30.8% patients remained to be on MV as a control regimen; 3 of them had highfre quency MV. SurfactantBL inhalation made it possible to change the respiratory support regimen and to reduce MV parame ters in these babies. 

  11. Towards the optimisation and adaptation of dry powder inhalers.

    Science.gov (United States)

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

    2014-08-15

    Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Antifibrinolytic mechanisms in acute airway injury after sulfur mustard analog inhalation.

    Science.gov (United States)

    Rancourt, Raymond C; Ahmad, Aftab; Veress, Livia A; Rioux, Jacqueline S; Garlick, Rhonda B; White, Carl W

    2014-10-01

    Acute lung injury in response to mustard gas (sulfur mustard [SM]) inhalation results in formation of fibrin casts, which obstruct the airway. The objective of this study was to identify fibrinolytic pathways that could be contributing to the persistence of airway casts after SM exposure. Rats were exposed to the SM analog, 2-chloroethyl ethyl sulfide, via nose-only aerosol inhalation. At 4 and 18 hours after exposure, animals were killed and airway-capillary leak estimated by measuring bronchoalveolar lavage fluid (BALF) protein and IgM content. The fibrin clot-degrading and plasminogen-activating capabilities of BALF were also assessed by activity assays, whereas Western blotting was used to determine the presence and activities of plasminogen activator inhibitor-1, thrombin activatable fibrinolytic inhibitor and α2-antiplasmin. Measurement of tissue-specific steady-state mRNA levels was also conducted for each fibrinolytic inhibitor to assess whether its synthesis occurs in lung or at extrapulmonary sites. The results of this study demonstrate that fibrin-degrading and plasminogen-activating capabilities of the airways become impaired during the onset of 2-chloroethyl ethyl sulfide-induced vascular leak. Findings of functionally active reservoirs of plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor, and α2-antiplasmin in BALF indicate that airway fibrinolysis is inhibited at multiple levels in response to SM.

  13. Indoor air condensate as a novel matrix for monitoring inhalable organic contaminants.

    Science.gov (United States)

    Roll, Isaac B; Halden, Rolf U; Pycke, Benny F G

    2015-05-15

    With the population of developed nations spending nearly 90% of their time indoors, indoor air quality (IAQ) is a critical indicator of human health risks from inhalation of airborne contaminants. We present a novel approach for qualitative monitoring of IAQ through the collection and analysis of indoor air condensate discharged from heat exchangers of heating, ventilation, and air conditioning (HVAC) systems. Condensate samples were collected from six suburban homes and one business in Maricopa County, Arizona, concentrated via solid-phase extraction, analyzed for 10 endocrine disrupting chemicals (EDCs) by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and screened for additional organic compounds by gas chromatography-mass spectrometry (GC-MS). All 10 EDCs were detected in at least one of the sampled buildings. More than 100 additional compounds were detected by GC-MS, of which 40 were tentatively identified using spectral database searches. Twelve compounds listed as designated chemicals for biomonitoring by the California Environmental Contaminant Biomonitoring Program were detected. Microfiltration of condensate samples prior to extraction had no discernable effect on contaminant concentration, suggesting that contaminants were freely dissolved or associated with inhalable, submicron particles. This study is the first to document the utility of HVAC condensate for the qualitative assessment of indoor air for pollutants. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Xenon-inhalation computed tomography for noninvasive quantitative measurement of tissue blood flow in pancreatic tumor.

    Science.gov (United States)

    Kubota, Masaru; Murakami, Takamichi; Nagano, Hiroaki; Eguchi, Hidetoshi; Marubashi, Shigeru; Kobayashi, Shogo; Wada, Hiroshi; Tanemura, Masahiro; Dono, Keizo; Nakamori, Shoji; Sakon, Masato; Monden, Morito; Mori, Masaki; Doki, Yuichiro

    2012-03-01

    The purpose of this prospective study was to demonstrate the ability to measure pancreatic tumor tissue blood flow (TBF) with a noninvasive method using xenon inhalation computed tomography (xenon-CT) and to correlate TBF with histological features, particularly microvascular density (MVD). TBFs of pancreatic tumors in 14 consecutive patients were measured by means of xenon-CT at diagnosis and following therapy. Serial abdominal CT scans were obtained before and after inhalation of nonradioactive xenon gas. TBF was calculated using the Fick principle. Furthermore, intratumoral microvessels were stained with anti-CD34 monoclonal antibodies before being quantified by light microscopy (×200). We evaluated MVD based on CD34 expression and correlated it with TBF. The quantitative TBF of pancreatic tumors measured by xenon CT ranged from 22.3 to 111.4 ml/min/100 g (mean ± SD, 59.6 ± 43.9 ml/min/100 g). High correlation (r = 0.885, P Xenon-CT is feasible in patients with pancreatic tumors and is able to accurately estimate MVD noninvasively.

  15. Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following Vicks inhaler use.

    Science.gov (United States)

    Poklis, A; Moore, K A

    1995-02-01

    The cross-reactivity of l-methamphetamine (l-desoxyephedrine) to the EMIT-d.a.u. class (EC) and EMIT-d.a.u. monoclonal amphetamine/methamphetamine (EM) assays was evaluated in urine specimens collected from six subjects using Vicks inhalers. The subjects were five men and a woman ranging from 27 to 47 years old. Four subjects used the inhaler as recommended by the manufacturer for five consecutive days; two subjects used double this dosage for three consecutive days. All urine voids were collected, totaling 132 specimens. All specimens were analyzed by the EC and EM assays. Specimens yielding a positive response were then analyzed by chiral and achiral gas chromatography/mass spectrometry (GC/MS). No specimen was positive by the EM assay, whereas 17 specimens yielded positive EC results. One subject for form the "as recommended" group had six positive specimens with maximum l-desoxyephedrine of 872 ng/ml. Both subjects using twice the recommended dosage had positive specimens, maximum l-desoxyephedrine of 1,560 ng/ml. No positive specimen contained > 200 ng/ml l-amphetamine.

  16. Measuring safety of inhaled corticosteroids in asthma.

    Science.gov (United States)

    Gerber, Anthony N

    2016-12-01

    Despite evidence demonstrating generally excellent therapeutic ratios for inhaled corticosteroids (ICSs) in asthma treatment, many clinicians and patients have ongoing concerns regarding their safety. To frame discussions of ICS safety, it is important to understand how safety is measured. To discuss how ICS safety is and should be measured. Discussion is augmented by relevant articles from the literature. The therapeutic value of corticosteroids depends on the activation and repression of thousands of genes. However, it is not fully known which genes cause the desirable, therapeutic effects and which cause the adverse effects. The drug development process attempts to elucidate the clinically significant therapeutic effects and adverse effects of a candidate molecule and then compare them to those of currently available corticosteroids. Approaches to monitoring safety include clinical trials, retrospective comparison to historical efficacy and safety data, surrogate markers, animal models, and in vitro assays. Both preclinical and clinical data are used to compare safety among corticosteroids; however, no specific pathway or model that can robustly predict therapeutic ratios has been identified. Furthermore, variation in adverse effects is influenced by isoforms of the glucocorticoid receptor, differences in corticosteroid characteristics, differences among patients, and environmental variation. Although some preclinical and patient-based metrics have predictive value, there is a clear need for improved biomarkers of corticosteroid adverse effects. Integrated analysis of preclinical and clinical data, including long-term safety data, could be used to address this important unmet need. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-07-25

    Inhaler errors are common amongst inhaler users. Therefore, in the development work of new inhalation devices, it is important to characterize the ease of use of the inhalers. In this study four dry powder inhalers, Diskus, Easyhaler, Ellipta and Turbuhaler, were evaluated, focusing on ease of use and patient preference. The study used a triangular methodology. The sample consisted of 31 inhaler naïve individuals. Educational videos for all inhalers were watched, and afterwards, the use of all four inhalers was demonstrated in a random order. The demonstrations were videotaped. Thereafter they were checked against a predefined checklist and all mistakes were recorded. Only 33% of inhaler demonstrations were completed without the participants making any mistakes. The proportions of subjects who used the devices correctly were as follows: Diskus 48%, Easyhaler 19%, Ellipta 55% and Turbuhaler 16%. When comparing correct and incorrect inhaler technique for each inhaler pair the following differences were statistically significant: Diskus vs. Easyhaler (pEllipta vs. Easyhaler (pEllipta vs. Turbuhaler (pEllipta, followed by Turbuhaler, were most often ranked as most preferred. Participants' preference of Ellipta over Easyhaler (p<0.01) and over Diskus (p<0.001) were statistically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Plasma biomarkers of oxidative stress: relationship to lung disease and inhaled nitric oxide therapy in premature infants.

    Science.gov (United States)

    Ballard, Philip L; Truog, William E; Merrill, Jeffrey D; Gow, Andrew; Posencheg, Michael; Golombek, Sergio G; Parton, Lance A; Luan, Xianqun; Cnaan, Avital; Ballard, Roberta A

    2008-03-01

    Inhaled nitric oxide treatment for ventilated premature infants improves survival without bronchopulmonary dysplasia. However, there has been no information regarding possible effects of this therapy on oxidative stress. We hypothesized that inhaled nitric oxide therapy would not influence concentrations of plasma biomarkers of oxidative stress. As part of the Nitric Oxide Chronic Lung Disease Trial, we collected blood samples at specified intervals from a subpopulation of 100 infants of score, and plasma carbonyl was positively correlated with severity score, supporting an association between oxidative stress and severity of lung disease. Infants who survived without bronchopulmonary dysplasia had 30% lower protein carbonylation concentrations at study entry than those who had an adverse outcome. At each of 3 time points (1-10 days) during exposure to study gas, there were no significant differences between control and treated infants for concentrations of plasma protein, 3-nitrotyrosine, and carbonylation. Inhaled nitric oxide treatment for premature infants who are at risk for bronchopulmonary dysplasia does not alter plasma biomarkers of oxidative stress, which supports the safety of this therapy.

  19. Use of a Remote Inhaler Monitoring Device to Measure Change in Inhaler Use with Chronic Obstructive Pulmonary Disease Exacerbations.

    Science.gov (United States)

    Sumino, Kaharu; Locke, Emily R; Magzamen, Sheryl; Gylys-Colwell, Ina; Humblet, Olivier; Nguyen, Huong Q; Thomas, Rachel M; Fan, Vincent S

    2017-10-16

    Remote inhaler monitoring is an emerging technology that enables the healthcare team to monitor the time and location of a patient's inhaler use. We assessed the feasibility of remote inhaler monitoring for chronic obstructive pulmonary disease (COPD) patients and the pattern of albuterol inhaler use associated with COPD exacerbations. Thirty-five participants with COPD used an electronic inhaler sensor for 12 weeks which recorded the date and time of each albuterol actuation. Self-reported COPD exacerbations and healthcare utilization were assessed monthly. We used generalized estimating equations with a logit link to compare the odds of an exacerbation day to a nonexacerbation day by the frequency of daily albuterol use. Average daily albuterol use on nonexacerbation days varied greatly between patients, ranging from 1.5 to 17.5 puffs. There were 48 exacerbation events observed in 29 participants during the study period, of which 16 were moderate-to-severe exacerbations. During the moderate-to-severe exacerbation days, the median value in average daily albuterol use increased by 14.1% (interquartile range: 2.7%-56.9%) compared to average nonexacerbation days. A 100% increase in inhaler use was associated with increased odds of a moderate-to severe exacerbation (odds ratio 1.54; 95% CI: 1.21-1.97). Approximately 74% of participants reported satisfaction with the sensor. The electronic inhaler sensor was well received in older patients with COPD over a 12-week period. Increased albuterol use captured by the device was associated with self-reported episodes of moderate-to-severe exacerbations.

  20. Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

    Directory of Open Access Journals (Sweden)

    Ashutosh Kale

    2010-01-01

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

  1. Accidental cutaneous burns secondary to salbutamol metered dose inhaler.

    Science.gov (United States)

    Kale, Ashutosh; Shackley, Fiona

    2010-01-01

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

  2. Dry powders for oral inhalation free of lactose carrier particles.

    Science.gov (United States)

    Healy, Anne Marie; Amaro, Maria Inês; Paluch, Krzysztof J; Tajber, Lidia

    2014-08-01

    Dry powder inhaler (DPI) products have traditionally comprised a simple formulation of micronised drug mixed with a carrier excipient, typically lactose monohydrate. The presence of the carrier is aimed at overcoming issues of poor flowability and dispersibility, associated with the cohesive nature of small, micronised active pharmaceutical ingredient (API) particles. Both the powder blend and the DPI device must be carefully designed so as to ensure detachment of the micronised drug from the carrier excipient on inhalation. Over the last two decades there has been a significant body of research undertaken on the design of carrier-free formulations for DPI products. Many of these formulations are based on sophisticated particle engineering techniques; a common aim in formulation design of carrier-free products being to reduce the intrinsic cohesion of the particles, while maximising dispersion and delivery from the inhaler. In tandem with the development of alternative formulations has been the development of devices designed to ensure the efficient delivery and dispersion of carrier-free powder on inhalation. In this review we examine approaches to both the powder formulation and inhaler design for carrier-free DPI products. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. [Inhalative application devices for patients suffering from asthma bronchiale].

    Science.gov (United States)

    Schwald, M; Schneider, A; Meyer, F J

    2006-06-01

    Asthma is a chronic inflammatory disorder of the airways. It is caused by infiltration of eosinophils, mast cells, and CD4+ -T-lymphocytes which leads to variable airway obstruction. The core element of therapy is to control inflammation, which is best possible with inhaled steroids, the so-called controller drugs. Cromones are only second line therapeutic agents because they are not powerful enough for optimal inflammation control. Reliever drugs like beta2-agonists or anticholinergic agents serve as a symptomatic medication because they only lead to bronchial dilatation. The inflammation in COPD is caused by neutrophils, macrophages and CD8+ -T-lymphocytes. This kind of inflammation causes an irreversible airway obstruction accompanied by destruction of the lung parenchyma. By the majority, only symptomatic medication is effective for COPD, like anticholinergic agents and beta2-agonists. About 10-20% of patients with COPD are showing improvement when treated with inhaled steroids. However, the best treatment result is only guaranteed by optimal application of the medication. The most important barrier is an insufficient coordination between manual use of the inhaling system and inhalation. Various attempts are made to solve this problem, thus leading to a huge variety of application systems. However this also leads to confusion of patients and doctors because it is difficult to choose the optimal system and to use it in the most efficient way. This article provides an overview of the different application systems and compiles important details to facilitate the optimal application of inhalation therapy by the patient.

  4. Urine concentrations of repetitive doses of inhaled salbutamol

    DEFF Research Database (Denmark)

    Elers, J; Pedersen, Lars; Henninge, J

    2011-01-01

    We examined blood and urine concentrations of repetitive doses of inhaled salbutamol in relation to the existing cut-off value used in routine doping control. We compared the concentrations in asthmatics with regular use of beta2-agonists prior to study and healthy controls with no previous use...... of beta2-agonists. We enrolled 10 asthmatics and 10 controls in an open-label study in which subjects inhaled repetitive doses of 400 microgram salbutamol every second hour (total 1600 microgram), which is the permitted daily dose by the World Anti-Doping Agency (WADA). Blood samples were collected...... at baseline, 30 min, 1, 2, 3, 4, and 6 h after the first inhalations. Urine samples were collected at baseline, 0-4 h, 4-8 h, and 8-12 h after the first inhalations. Median urine concentrations peaked in the period 4-8 h after the first inhalations in the asthmatics and between 8-12 h in controls...

  5. Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    2015-07-01

    Full Text Available Increasing use of engineered nanomaterials (ENMs in consumer products may result in widespread human inhalation exposures. Due to their high surface area per unit mass, inhaled ENMs interact with multiple components of the pulmonary system, and these interactions affect their ultimate fate in the body. Modeling of ENM transport and clearance in vivo has traditionally treated tissues as well-mixed compartments, without consideration of nanoscale interaction and transformation mechanisms. ENM agglomeration, dissolution and transport, along with adsorption of biomolecules, such as surfactant lipids and proteins, cause irreversible changes to ENM morphology and surface properties. The model presented in this article quantifies ENM transformation and transport in the alveolar air to liquid interface and estimates eventual alveolar cell dosimetry. This formulation brings together established concepts from colloidal and surface science, physics, and biochemistry to provide a stochastic framework capable of capturing essential in vivo processes in the pulmonary alveolar lining layer. The model has been implemented for in vitro solutions with parameters estimated from relevant published in vitro measurements and has been extended here to in vivo systems simulating human inhalation exposures. Applications are presented for four different ENMs, and relevant kinetic rates are estimated, demonstrating an approach for improving human in vivo pulmonary dosimetry.

  6. Moving from CFC aerosol to HFA aerosol or dry powder inhalers: what do patients think?

    Science.gov (United States)

    Hartung, Thomas K; Allbutt, Helen; Dewar, Maria; Innes, J Alastair; Crompton, Graham K

    2002-01-01

    Environmentally friendly hydrofluoroalkane (HFA) pressurised metered-dose inhalers are currently being marketed to replace chlorofluorocarbon (CFC)-driven devices. It is uncertain whether these new formulations with different properties are acceptable to patients. Similarly, switching a patient to a dry powder inhaler (DPI) carries the risk of non-acceptance. One hundred patients with obstructive airway disease on regular CFC aerosol inhaler medication underwent a standardised, structured interview. During the interview patients were asked to use a new HFA aerosol inhaler and three DPIs in random order. Patients' notions were recorded. Most patients (96) agreed to change from their CFC to the HFA inhaler, of those, only 12 did so with some reservation. Properties (taste, user-friendliness, design) of the HFA inhaler were rated favourably. DPIs represented an acceptable alternative to aerosol inhalers. In fact, 57 patients preferred a DPI over the HFA inhaler. Not all powder devices were equally acceptable. Replacing the CFC inhaler with patients' preferred alternative devices resulted in a more than 3-fold increase in costs. Concerns about the acceptability of reformulated CFC-free aerosol inhalers are ill founded. However, if given the choice, many patients prefer a DPI over the HFA inhaler. The transition offers an opportunity to review patients' current treatment and the proficiency of their inhaling technique. Moving to CFC-free inhalers will have revenue implications. Copyright 2002 S. Karger AG, Basel

  7. Influences of gender and anthropometric features on inspiratory inhaler acoustics and peak inspiratory flow rate.

    Science.gov (United States)

    Taylor, Terence E; Holmes, Martin S; Sulaiman, Imran; Costello, Richard W; Reilly, Richard B

    2015-01-01

    Inhalers are hand-held devices used to treat chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Medication is delivered from an inhaler to the user through an inhalation maneuver. It is unclear whether gender and anthropometric features such as age, height, weight and body mass index (BMI) influence the acoustic properties of inspiratory inhaler sounds and peak inspiratory flow rate (PIFR) in inhalers. In this study, healthy male (n=9) and female (n=7) participants were asked to inhale at an inspiratory flow rate (IFR) of 60 L/min in four commonly used inhalers (Turbuhaler(™), Diskus(™), Ellipta(™) and Evohaler(™)). Ambient inspiratory sounds were recorded from the mouthpiece of each inhaler and over the trachea of each participant. Each participant's PIFR was also recorded for each of the four inhalers. Results showed that gender and anthropometric features have the potential to influence the spectral properties of ambient and tracheal inspiratory inhaler sounds. It was also observed that males achieved statistically significantly higher PIFRs in each inhaler in comparison to females (p<;0.05). Acoustic features were found to be significantly different across inhalers suggesting that acoustic features are modulated by the inhaler design and its internal resistance to airflow.

  8. Popcorn flavoring effects on reactivity of rat airways in vivo and in vitro.

    Science.gov (United States)

    Zaccone, Eric J; Thompson, Janet A; Ponnoth, Dovenia S; Cumpston, Amy M; Goldsmith, W Travis; Jackson, Mark C; Kashon, Michael L; Frazer, David G; Hubbs, Ann F; Shimko, Michael J; Fedan, Jeffrey S

    2013-01-01

    "Popcorn workers' lung" is an obstructive pulmonary disease produced by inhalation of volatile artificial butter flavorings. In rats, inhalation of diacetyl, a major component of butter flavoring, and inhalation of a diacetyl substitute, 2,3-pentanedione, produce similar damage to airway epithelium. The effects of diacetyl and 2,3-pentanedione and mixtures of diacetyl, acetic acid, and acetoin, all components of butter flavoring, on pulmonary function and airway reactivity to methacholine (MCh) were investigated. Lung resistance (RL) and dynamic compliance (Cdyn) were negligibly changed 18 h after a 6-h inhalation exposure to diacetyl or 2,3-pentanedione (100-360 ppm). Reactivity to MCh was not markedly changed after diacetyl, but was modestly decreased after 2,3-pentanedione inhalation. Inhaled diacetyl exerted essentially no effect on reactivity to mucosally applied MCh, but 2,3-pentanedione (320 and 360 ppm) increased reactivity to MCh in the isolated, perfused trachea preparation (IPT). In IPT, diacetyl and 2,3-pentanedione (≥3 mM) applied to the serosal and mucosal surfaces of intact and epithelium-denuded tracheas initiated transient contractions followed by relaxations. Inhaled acetoin (150 ppm) exerted no effect on pulmonary function and airway reactivity in vivo; acetic acid (27 ppm) produced hyperreactivity to MCh; and exposure to diacetyl + acetoin + acetic acid (250 + 150 + 27 ppm) led to a diacetyl-like reduction in reactivity. Data suggest that the effects of 2,3-pentanedione on airway reactivity are greater than those of diacetyl, and that flavorings are airway smooth muscle relaxants and constrictors, thus indicating a complex mechanism.

  9. Pulmonary Alveolar Proteinosis in Setting of Inhaled Toxin Exposure and Chronic Substance Abuse

    Directory of Open Access Journals (Sweden)

    Meirui Li

    2018-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare lung disorder in which defects in alveolar macrophage maturation or function lead to the accumulation of proteinaceous surfactant in alveolar space, resulting in impaired gas exchange and hypoxemia. PAP is categorized into three types: hereditary, autoimmune, and secondary. We report a case of secondary PAP in a 47-year-old man, whose risk factors include occupational exposure to inhaled toxins, especially aluminum dust, the use of anabolic steroids, and alcohol abuse, which in mice leads to alveolar macrophage dysfunction through a zinc-dependent mechanism that inhibits granulocyte macrophage-colony stimulating factor (GM-CSF receptor signalling. Although the rarity and vague clinical presentation of PAP can pose diagnostic challenges, clinician awareness of PAP risk factors may facilitate the diagnostic process and lead to more prompt treatment.

  10. Acute lung injury after inhalation of water-proofing spray while smoking a cigarette.

    Science.gov (United States)

    Jinn, Y; Akizuki, N; Ohkouchi, M; Inase, N; Ichioka, M; Marumo, F

    1998-01-01

    A 34-year-old Japanese woman developed acute lung injury soon after inhaling a water-proofing spray which she applied onto her ski suit while smoking a cigarette at the same time. She initially demonstrated arterial hypoxemia (PaO2 = 59 mm Hg) and ground-glass opacities in both lung fields on the CT scan, which both returned to normal without any medication. Several water-proofing sprays, which are easily obtainable in Japan, contain 1,1,1-trichloroethane, liquefied petroleum gas and fluoride resin. Although these components have not been reported to be toxic to the lung yet, high concentrations of these components and/or the pyrolytic products of fluoride resin may have caused acute lung injury in this case.

  11. Effect of inhaled terbutaline on substrate utilization and 300-kcal time trial performance

    DEFF Research Database (Denmark)

    Kalsen, Anders; Hostrup, Morten; Karlsson, Sebastian

    2014-01-01

    In a randomized double-blind crossover design, we investigated the effect of the beta2-agonist terbutaline on endurance performance and substrate utilization in nine moderately trained males (maximum oxygen uptake (VO2max): 58.9±3.1 mL min(-1) kg(-1)). Subjects performed 60 min of submaximal...... exercise (65-70% of VO2max) immediately followed by a 300-kcal time trial with inhalation of either terbutaline (TER) or placebo (PLA). Pulmonary gas exchange was measured during the submaximal exercise and muscle biopsies were collected before and after the exercise bouts. Time trial performance...... performance, but increase carbohydrate metabolism in skeletal muscles during submaximal exercise independent of AMPK and ACC phosphorylation, and that this effect diminishes as drug exposure time, exercise duration and intensity are increased....

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

    Science.gov (United States)

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

    2017-10-01

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

  13. Development of inhalable formulations of anti-inflammatory drugs to potentially treat smoke inhalation injury in burn victims.

    Science.gov (United States)

    Thai, A; Xiao, J; Ammit, A J; Rohanizadeh, R

    2010-04-15

    Injury arising from smoke inhalation is a significant mortality risk in severe burned patients. Inflammatory processes are major contributors to the development of respiratory insufficiency owing to pulmonary oedema, formation of airway fibrin clots and hypoxaemia. Anti-inflammatory and anti-coagulant drugs such as heparin and pentoxifylline are currently systemically administered for the treatment of smoke inhalation. Delivery of these drugs in the form of inhalable particles could be an effective manner to achieve rapid targeted action for acceleration of the treatment. The study developed and characterised a series of spray-dried heparin and pentoxifylline dry powder formulations suitable for inhalation administration. Drug particles were co-spray-dried with leucine in varying ratios. Particle size analysis confirmed all powders (except 2%, w/w, pentoxifylline with 1%, w/w, leucine in spray-drying feed solution) had particle size in the optimal range (heparin surface topography while pentoxifylline formulations were a mixture of elongated needles interspersed with wrinkly particles. Addition of leucine improved fine particle fraction of heparin and pentoxifylline. The study indicated manufacture of inhalable heparin and pentoxifylline was feasible and can potentially be an attractive delivery alternative to the more conventional systemic delivery route. Copyright 2010 Elsevier B.V. All rights reserved.

  14. In vitro Cell Culture Model for Toxic Inhaled Chemical Testing

    Science.gov (United States)

    Ahmad, Shama; Ahmad, Aftab; Neeves, Keith B.; Hendry-Hofer, Tara; Loader, Joan E.; White, Carl W.; Veress, Livia

    2014-01-01

    Cell cultures are indispensable to develop and study efficacy of therapeutic agents, prior to their use in animal models. We have the unique ability to model well differentiated human airway epithelium and heart muscle cells. This could be an invaluable tool to study the deleterious effects of toxic inhaled chemicals, such as chlorine, that can normally interact with the cell surfaces, and form various byproducts upon reacting with water, and limiting their effects in submerged cultures. Our model using well differentiated human airway epithelial cell cultures at air-liqiuid interface circumvents this limitation as well as provides an opportunity to evaluate critical mechanisms of toxicity of potential poisonous inhaled chemicals. We describe enhanced loss of membrane integrity, caspase release and death upon toxic inhaled chemical such as chlorine exposure. In this article, we propose methods to model chlorine exposure in mammalian heart and airway epithelial cells in culture and simple tests to evaluate its effect on these cell types. PMID:24837339

  15. Adolescents and inhalant abuse: how huffing affects the myelin sheath.

    Science.gov (United States)

    Baird, Carolyn A; Furek, Maxim W

    2012-05-01

    As concern grows over the impact that accidental chemical exposures may have on the long term health of individuals, our young people are deliberately exposing themselves to the effect of neurotoxic chemicals with the intent of feeling high. Over time the result of inhaling these chemicals is often the development of symptoms and behavior that may suggest serious physiological damage. Research is being conducted to examine what the exact nature of the damage might be, especially the impact of inhaled lipophilic chemicals on structures in the brain and other parts of the nervous system. Healthcare professionals responsible for assessing adolescents in all settings need to be aware of the prevalence of inhalant abuse, as well as the chemicals, terminology, and potential symptomatology in order to intervene in the behavior and provide diagnosis and treatment as indicated. Some implications for nursing are included.

  16. Adherence to inhaled therapy, mortality and hospital admission in COPD

    DEFF Research Database (Denmark)

    Vestbo, J; Anderson, J A; Calverley, P M A

    2009-01-01

    BACKGROUND: Little is known about adherence to inhaled medication in chronic obstructive pulmonary disease (COPD) and the impact on mortality and morbidity. METHODS: Data on drug adherence from a randomised double-blind trial comparing inhaled salmeterol 50 microg + fluticasone propionate 500...... as an ancillary study. RESULTS: Of the 4880 patients (79.8%) with good adherence defined as >80% use of study medication, 11.3% died compared with 26.4% of the 1232 patients (20.2%) with poor adherence. The annual rates of hospital admission for exacerbations were 0.15 and 0.27, respectively. The association...... was more pronounced in patients with good adherence than in those with poor adherence. CONCLUSION: Adherence to inhaled medication is significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD. Further research is needed to understand these strong...

  17. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...... findings, health status, and dyspnea were also monitored. RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD...

  18. Ingestive and inhalative allergy to the mushroom Boletus edulis.

    Science.gov (United States)

    Torricelli, R; Johansson, S G; Wüthrich, B

    1997-07-01

    This is the first report on inhalative and ingestive allergy to the common edible mushroom Boletus edulis (Be) (English, edible boletus; German, Steinpilz; French, bolet; Italian, porcino or boleto) belonging to the class Basidiomycetes. Four cases observed in our allergy unit are presented, showing different clinical manifestations of this rare allergy: as an occupational problem or life-threatening anaphylactic reactions after eating Be. In all cases, skin prick-to-prick tests with raw Be were strongly positive: in three cases, specific IgE against Be could be found. The symptoms were reproducible after an inhalation challenge test. It is noteworthy that not only can Basidiomycetes cause airborne allergy but also that edible mushrooms from this class can cause inhalative and intestinal allergy. The two patients with strong anaphylactic reactions demonstrate that Be may have great allergenic potential.

  19. Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation.

    Science.gov (United States)

    Enkhbaatar, Perenlei; Cox, Robert A; Traber, Lillian D; Westphal, Martin; Aimalohi, Esechie; Morita, Naoki; Prough, Donald S; Herndon, David N; Traber, Daniel L

    2007-12-01

    Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots. Prospective, randomized, controlled, experimental animal study. Investigational intensive care unit at a university hospital. Adult female sheep. After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury. Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology. The results provide definitive evidence that aerosolized rhAT and

  20. Gas gangrene

    Science.gov (United States)

    Tissue infection - Clostridial; Gangrene - gas; Myonecrosis; Clostridial infection of tissues; Necrotizing soft tissue infection ... Gas gangrene is most often caused by bacteria called Clostridium perfringens. It also can be caused by ...

  1. Particle exposure and inhaled dose during commuting in Singapore

    Science.gov (United States)

    Tan, Sok Huang; Roth, Matthias; Velasco, Erik

    2017-12-01

    Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

  2. Inhalation of tobramycin using simulated cystic fibrosis patient profiles.

    Science.gov (United States)

    Haynes, Alfred; Geller, David; Weers, Jeffry; Ament, Brian; Pavkov, Richard; Malcolmson, Richard; Debonnett, Laurie; Mastoridis, Paul; Yadao, Anthony; Heuerding, Silvia

    2016-11-01

    TOBI(®) Podhaler™ is a capsule-based drug-device combination (tobramycin inhalation powder [TIP] 28 mg capsules via unit-dose dry powder T-326 Inhaler [Podhaler™]) developed for treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF). We explored how inspiratory flow profiles and mouth-throat geometries affect drug delivery with the T-326 Inhaler. Inspiratory flow profiles were recorded from 38 subjects aged 6-71 who had CF and varying degrees of lung function impairment. Ten of the inspiratory flow profiles were simulated in the laboratory using a custom breath simulator to determine delivered dose (DD) from the T-326 Inhaler. In vitro total lung dose (TLDin vitro ) was measured using four anatomical throat models, ranging from a child to a large adult. Aerosol performance was assessed across a range of inspiratory flow profiles. Mean DD ranged from 88.8% to 97.0% of declared capsule content. TLDin vitro ranged from 54.8% to 72.4% of capsule content between the flow profile/throat options tested, and the mean TLDin vitro across the range of flow profiles and anatomical throats tested was 63 ± 5%. Our findings indicate that the T-326 Inhaler provides reliable drug delivery at flow rates likely to be achieved by a broad spectrum of patients with CF. Importantly, forceful inhalation was not required to achieve a robust TLDin vitro . Pediatr Pulmonol. 2016;51:1159-1167. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Challenges in inhaled product development and opportunities for open innovation.

    Science.gov (United States)

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

    2011-01-01

    Dosimetry, safety and the efficacy of drugs in the lungs are critical factors in the development of inhaled medicines. This article considers the challenges in each of these areas with reference to current industry practices for developing inhaled products, and suggests collaborative scientific approaches to address these challenges. The portfolio of molecules requiring delivery by inhalation has expanded rapidly to include novel drugs for lung disease, combination therapies, biopharmaceuticals and candidates for systemic delivery via the lung. For these drugs to be developed as inhaled medicines, a better understanding of their fate in the lungs and how this might be modified is required. Harmonized approaches based on 'best practice' are advocated for dosimetry and safety studies; this would provide coherent data to help product developers and regulatory agencies differentiate new inhaled drug products. To date, there are limited reports describing full temporal relationships between pharmacokinetic (PK) and pharmacodynamic (PD) measurements. A better understanding of pulmonary PK and PK/PD relationships would help mitigate the risk of not engaging successfully or persistently with the drug target as well as identifying the potential for drug accumulation in the lung or excessive systemic exposure. Recommendations are made for (i) better industry-academia-regulatory co-operation, (ii) sharing of pre-competitive data, and (iii) open innovation through collaborative research in key topics such as lung deposition, drug solubility and dissolution in lung fluid, adaptive responses in safety studies, biomarker development and validation, the role of transporters in pulmonary drug disposition, target localisation within the lung and the determinants of local efficacy following inhaled drug administration. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD

    DEFF Research Database (Denmark)

    Crim, Courtney; Dransfield, Mark T; Bourbeau, Jean

    2015-01-01

    RATIONALE: Radiographically confirmed pneumonia risk with inhaled corticosteroid use in chronic obstructive pulmonary disease (COPD) has not been assessed to date. OBJECTIVES: To determine the incidence of pneumonia, risk factors, and clinical attributes with inhaled fluticasone furoate (FF...

  5. Study the effects of radon inhalation on biomechanical properties of blood in rats

    Directory of Open Access Journals (Sweden)

    Mostafa Fawzy Eissa

    2015-09-01

    Full Text Available Purpose: To investigate the effect of inhalation radon gas (Rn on the biomechanical properties of red blood cell of rats. Methods: 20 young healthy adult male albino rats were divided into equally 4 groups. The first group (0 served as control group, while the other three groups (I, II and III were exposed to Rn gas inside a chamber for 3, 5 and 7 weeks. The biomechanical properties of red blood cell of rats was performed by determine the rheological properties of blood and the osmotic fragility of red blood cells (RBCs. Results: The Rn doses received by every group of rats were found to 34.84, 58.07 and 81.30 mSv for 3, 5 and 7 weeks respectively (based on 12 exposure hours per week. The obtained results indicate that the viscosity, consistency index, yield stress and aggregation index increase with Rn doses. The osmotic fragility curves of irradiated groups shift toward lower values of NaCl concentration. The dispersion of hemolysis (S increased, at the same time an average osmotic fragility (H50% decreased. Conclusion: The results indicates that the exposure to radon alters the mechanical properties of red blood cells membrane (permeability and elasticity reflecting a change in its physiological properties. This mean that low levels of Rn gas are harmful to biological systems and the degree of damage was dose-dependent.

  6. Lung deposition of inhaled drugs increases with age

    DEFF Research Database (Denmark)

    Onhøj, J; Thorsson, L; Bisgaard, H

    2000-01-01

    Budesonide plasma concentrations after inhalation of a fixed dose of the drug from a pressurized metered dose inhaler (pMDI) with spacer (Nebuchamber) were compared in young children and adults: 26 patients with mild asthma comprising 8 children 2-3 yr, 8 children 4-6 yr, and 10 adults 20-41 yr....... Budesonide 2 x 200 microg was given by pMDI via Nebuchamber with mouthpiece and noseclip. Children of 2-3 yr used a facemask. Plasma was collected regularly for 8 h after drug administration. Budesonide was measured by liquid chromatography plus tandem mass spectrometry. The dose to patient was estimated...

  7. Non-CFC metered dose inhalers: the patent landscape.

    Science.gov (United States)

    Bowman, P A; Greenleaf, D

    1999-09-10

    There have been many patent applications to the European Patent Office over the past decade involving the transition of pressurised metered dose inhalers from the CFCs to non-CFC propellants. In addition to those where formulations are changed, there are those relating to specific drugs or drug classes, processes of manufacture and modifications to the container/closure system. Many of these have been opposed, usually on the grounds of obviousness. However, due to the length of time for the opposition process and the fact that there are few non-CFC pressurised inhalers on the market yet, the complete picture of which patents are valid has yet to unfold.

  8. Intermittent inhaled corticosteroids in infants with episodic wheezing

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  9. Patients with COPD have low adherence to inhaled medicine

    DEFF Research Database (Denmark)

    Lange, Peter; Toettenborg, Sandra; Topp, Marie

    2014-01-01

    Medicine adherence in patients with obstructive pulmonary disease (COPD), has not been studied in Denmark. Studies from other countries, however, unequivocally report low prevalence of patients who follow their doctor's advice and have sufficient adherence to inhaled medicine. In this review we...... describe results of previous studies on prevalence of adherence to inhaled medicine in COPD, and define characteristics of the patients and treatment associated with degree of adherence. We conclude that health professionals should always consider non-adherence, strive to simplify regiments......, and that there is an urgent need of studies aiming at improving adherence in patients with COPD....

  10. A perspective on the developmental toxicity of inhaled nanoparticles

    DEFF Research Database (Denmark)

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

    2015-01-01

    This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respirat......This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from...

  11. Implicit memory for stimuli presented during inhalation anesthesia in children.

    Science.gov (United States)

    Kalff, A C; Bonke, B; Wolters, G; Manger, F W

    1995-10-01

    During general inhalation anesthesia, neutral phrases including either the color blue or yellow combined with one of two objects, ball or kite, were repeatedly presented to 36 children undergoing eye surgery. Postoperative testing with a coloring and two-choice task was performed to detect preferences for the colors and objects presented under anesthesia. No preference attributable to implicit memory could be demonstrated, and there was no explicit recollection of intraoperative events. Memory of intraoperative events occurring during inhalation anesthesia was not demonstrated with the present methodology in young children.

  12. Inhaled furosemide is not effective in severe asthma in children

    OpenAIRE

    Matsumoto, Tomoaki; Muraoka, Norimasa; Ogawa, Masakatsu; Matsui, Mika; Tajima, Seiki; Miike, Teruhisa

    2000-01-01

    The purpose of the present study was to determine whether or not inhaled furosemide has any therapeutic benefit in acute asthma in children. Aerosolized furosemide (20 mg) was administered four times per day together with conventional asthma therapy for 2 days in five children with severe asthma exacerbation. The oxygen saturation with a pulse oximeter (SpO2), and the peak expiratory flow (PEF) were measured before and 10 min after furosemide inhalation. Although a little improvement in SpO2 ...

  13. Comparison of absorption after inhalation and installation of uranium octoxide

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-01

    Values for the absorption parameters were compared after inhalation or intratracheal installation of 1.5 {mu}m mass median aerodynamic diameter (MMAD) {sup 233}U{sub 3}O{sub 8} particles into the lungs of HMT strain rats. The two sets of parameter values were similar, as were the calculated dose coefficients and predicted biokinetics for workers. Hence the inhalation and installation techniques can probably both be used to generate values of the absorption parameters for U{sub 3}O{sub 8}. (author)

  14. Use of Mannitol Inhalation Challenge in Assessment of Cough

    Science.gov (United States)

    2009-01-01

    Bronchial provocation testing uses a variety of direct and indirect inhalational challenges to evaluate airway hyperreactivity. Mannitol, a simple, easy-to-administer hypertonic stimulus available in many countries, is currently under review by the FDA in the US. Healthy subjects show no airway response to inhaled mannitol; asthmatic patients respond with airway narrowing similar to challenges with hypertonic saline and exercise. Mannitol challenge also has a tussive effect that is independent of bronchoconstriction, suggesting different physiologic pathways. Patients with chronic cough show increased sensitivity to mannitol, and mannitol testing may be useful for evaluating heterogeneity in the cough response. PMID:19756864

  15. Inhalable Spray-Freeze-Dried Powder with L-Leucine that Delivers Particles Independent of Inspiratory Flow Pattern and Inhalation Device.

    Science.gov (United States)

    Otake, Hiroko; Okuda, Tomoyuki; Hira, Daiki; Kojima, Haruyoshi; Shimada, Yasuhiro; Okamoto, Hirozazu

    2016-04-01

    The purpose of this study was to develop inhalable particles that can reach deep into the lungs efficiently independent of inhalation patterns of patients and inhalation devices. We prepared porous particles including L-leucine (Leu), a dispersive agent, by a spray-freeze-drying (SFD) method and examined the influence of inspiratory flow patterns and inhalation devices with various inhalation resistances. Four types of SFD powder with different Leu contents (0-10%) were prepared. Scanning electron microscopy and laser diffraction were used to measure the morphology and size distribution of the powders. In-vitro inhalation characteristics were determined using a twin-stage liquid impinger equipped with an inspiratory flow pattern simulator. The effects of Leu on the adhesion force and electrostatic property of the particles were evaluated. The inhalation performance of the powders was improved by the addition of Leu. The powders with Leu showed a high inhalation performance regardless of inspiratory flow patterns and devices. The addition of Leu decreased the adhesion force and increased the surface potential of the powders. The SFD particles with Leu showed high inhalation performance regardless of the inhalation patterns and devices, which was attributed to the decreased adhesion force between particles and increased dispersibility.

  16. Oscillation after inhalation: high frequency oscillatory ventilation in burn patients with the acute respiratory distress syndrome and co-existing smoke inhalation injury.

    Science.gov (United States)

    Cartotto, Robert; Walia, Gautam; Ellis, Sandi; Fowler, Rob

    2009-01-01

    The purpose of this study was to evaluate the effectiveness of, and complications associated with High Frequency Oscillatory Ventilation (HFOV) in burn patients with the Acute Respiratory Distress Syndrome (ARDS) who have had a smoke inhalation injury, and to compare with those without an inhalation injury. Burn patients with progressive oxygenation failure from ARDS while on conventional mechanical ventilation were placed on HFOV as a "rescue" ventilation modality. There were 19 patients with burn + inhalation injury and 30 patients with burn only. Burned patients with ARDS but without inhalation injury had significant temporal improvement in the oxygenation index from 27 +/- 8 on conventional mechanical ventilation to 17 +/- 6 within 48 hours of initiating HFOV. However, burned patients with ARDS and smoke inhalation injury did not achieve significant or even eventual improvements in oxygenation index with HFOV. There was also a trend towards higher rates of early HFOV failure and severe hypercapnia while on HFOV among the patients with inhalation injury. Delivery of nebulized bronchodilators, heparin and n-acetyl cysteine, normally mainstays of smoke inhalation therapy, was impossible during HFOV. The presence of a smoke inhalation injury appears to impair the response to HFOV when this ventilation modality is instituted for ARDS-related oxygenation failure. Severe hypercapnia tended to be more frequent during HFOV among patients with smoke inhalation. These findings, combined with the difficulties in delivery of nebulized medications during HFOV suggest that HFOV may not be the optimal "rescue" ventilation modality in cases of ARDS if there has been an inhalation injury.

  17. An assessment of a new breath actuated inhaler device in acutely wheezy children.

    OpenAIRE

    Ruggins, N R; Milner, A. D.; Swarbrick, A

    1993-01-01

    A randomised double blind, two period cross over study was designed to compare the ability of 51 hospitalised asthmatics with acute exacerbations to use each of two inhalers. The inhalers compared were a new breath actuated metered dose inhaler, the Autohaler inhalation device, and a dry powder device, the Rotahaler. Preassessment data included the measurement of peak inspiratory flow rate (PIFR), peak expiratory flow rate (PEFR), pulse rate, and oxygen saturation. Therapeutic response to eac...

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

    Science.gov (United States)

    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

  19. Does a Nebulized Heparin/N-acetylcysteine Protocol Improve Outcomes in Adult Smoke Inhalation?

    OpenAIRE

    Natalie S. Kashefi, MS; Jonathan I. Nathan, MD, MBA; Sharmila Dissanaike, MD, FACS

    2014-01-01

    Background: Smoke inhalation is a major source of morbidity and mortality. Heparin and N-acetylcysteine treatment has potential efficacy in inhalation injury. We investigated the impact of a heparin/N-acetylcysteine/albuterol nebulization protocol in adult patients with inhalation injury. Methods: A retrospective review was performed of adult inhalation injury patients, admitted to a regional burn center between January 2011 and July 2012, who underwent a protocol of alternating treatments of...

  20. Laboratory approach for diagnosis of toluene-based inhalant abuse in a clinical setting

    Directory of Open Access Journals (Sweden)

    Raka Jain

    2016-01-01

    Full Text Available The steady increase of inhalant abuse is a great challenge for analytical toxicologists. This review describes an overview of inhalant abuse including the extent of the problem, types of products abused, modes of administration, pharmacology and effects of inhalants, the role of laboratory, interpretation of laboratory results and clinical considerations. Regular laboratory screening for inhalant abuse as well as other substance abuse and health risk behaviors must be a part of standard clinical care.

  1. Effectiveness of the different methods of inhalation drugs delivery in children with bronchial asthma

    Directory of Open Access Journals (Sweden)

    S.M. Nedelska

    2017-03-01

    Full Text Available Aim of the work — to evaluate the effectiveness of inhalation technique when using different types of inhalers (dry powder inhalers — Turbuhaler, Diskus, metered-dose inhalers, breath-actuated inhalers — Easyhaler. Materials and methods. 45 patients aged 6–17 years underwent the evaluation of inhalation technique accuracy with the use of In-Check-Dial — apparatus, which imitates the airway resistance that should be overcome during inspiration through different inhaler types, and measure inspiration velocity. Incidence of mistakes was studied in different age groups. Results. 80 % of children aged 6–7 years made mistakes while using Turbuhaler, 73.3 % — metered-dose inhaler, 60 % — Easyhaler. There were no mistakes in patients making inhalation by means of Diskhaler. 100 % of children aged 12–14 years incorrectly used metered-dose inhaler. Easyhaler was incorrectly used in 66.6 % of cases, Diskhaler — in 26.6 %. Among elder group, incidence of mistakes when making inhalations through Turbuhaler was lower — 40 % in 12–14-year-old group and 25 % — in 15–17-year-old (р < 0.05. Children of 15–17 years old are able to use Turbuhaler and Diskus (mistakes in 33.3 and 46.6 %, respectively. At the same time, none of the patients have done the correct inhalation by means of metered-dose inhaler, 93.3 % of the patients have mistakes when using Easyhaler. Conclusions. The incidence of mistakes depends on the age and inhaler type and reaches 26–100 %. Minimal quantity of mistakes is seen for Diskus (in all age groups, maxi­mal — for metered-dose inhaler. For the purpose of optimal inhaler choice in a child with bronchial asthma, it is advisable to measure the inspiratory flow with the help of In-Check-Dial before therapy administration.

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

    Science.gov (United States)

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

    1990-06-01

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

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

    Science.gov (United States)

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

    1990-01-01

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

  4. 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

    OpenAIRE

    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 lea...

  5. The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder.

    Science.gov (United States)

    Yang, Michael Y; Verschuer, Jordan; Shi, Yuyu; Song, Yang; Katsifis, Andrew; Eberl, Stefan; Wong, Keith; Brannan, John D; Cai, Weidong; Finlay, Warren H; Chan, Hak-Kim

    2016-11-20

    The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with 99m Tc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50-70L/min to 110-130L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R 2 =1.0). On the other hand, the PI had a stronger association with the MMAD (R 2 =1.0) than the FPF (R 2 =0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Ruslands Gas

    OpenAIRE

    Elkjær, Jonas Bondegaard

    2008-01-01

    This paper is about Russian natural gas and the possibility for Russia to use its reserves of natural gas politically towards the European Union to obtain some political power. Russia owns 32,1 % of the world gas reserves, and The European Union is getting 50 % of its gas import from Russia. I will use John Mearsheimer’s theory ”The Tragedy of Great Power Politics” to explain how Russia can use its big reserves of gas on The European Union to get political influence.

  7. Knowledge of actions of inhaled corticosteroids in patients who did not persist drug treatment early

    NARCIS (Netherlands)

    Menckeberg, T.T.; Hugtenburg, J.G.; Lammers, J.W.; Raaijmakers, J.A.; Bouvy, M.L.

    2012-01-01

    Objective To evaluate, among new users of inhaled corticosteroids that did not persist treatment, knowledge of inhaled corticosteroids' actions and whether they were instructed on the use of their inhaler. Setting Fifteen community pharmacies in The Netherlands. Methods Patients were interviewed by

  8. Effectiveness of Same Versus Mixed Asthma Inhaler Devices : A Retrospective Observational Study in Primary Care

    NARCIS (Netherlands)

    Price, David; Chrystyn, Henry; Kaplan, Alan; Haughney, John; Roman-Rodriguez, Miguel; Burden, Annie; Chisholm, Alison; Hillyer, Elizabeth V.; von Ziegenweidt, Julie; Ali, Muzammil; van der Molen, Thys

    Purpose: Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the

  9. Trends in the technology-driven development of new inhalation devices

    NARCIS (Netherlands)

    Frijlink, Erik; de Boer, A.H

    2005-01-01

    Inhalation technology diverges rapidly along various lines. A variety of technological solutions are currently under development to overcome the many problems related to adequate aerosol generation both for dry powder inhalation systems and for liquid inhalation systems. Many of the improvements are

  10. Effectiveness and success factors of educational inhaler technique interventions in asthma & COPD patients: a systematic review.

    Science.gov (United States)

    Klijn, Sven L; Hiligsmann, Mickaël; Evers, Silvia M A A; Román-Rodríguez, Miguel; van der Molen, Thys; van Boven, Job F M

    2017-04-13

    With the current wealth of new inhalers available and insurance policy driven inhaler switching, the need for insights in optimal education on inhaler use is more evident than ever. We aimed to systematically review educational inhalation technique interventions, to assess their overall effectiveness, and identify main drivers of success. Medline, Embase and CINAHL databases were searched for randomised controlled trials on educational inhalation technique interventions. Inclusion eligibility, quality appraisal (Cochrane's risk of bias tool) and data extraction were performed by two independent reviewers. Regression analyses were performed to identify characteristics contributing to inhaler technique improvement. Thirty-seven of the 39 interventions included (95%) indicated statistically significant improvement of inhaler technique. However, average follow-up time was relatively short (5 months), 28% lacked clinical relevant endpoints and all lacked cost-effectiveness estimates. Poor initial technique, number of inhalation procedure steps, setting (outpatient clinics performing best), and time elapsed since intervention (all, p education group size (individual vs. group training) and inhaler type (dry powder inhalers vs. pressurised metered dose inhalers) did not play a significant role. Notably, there was a trend (p = 0.06) towards interventions in adults being more effective than those in children and the intervention effect seemed to wane over time. In conclusion, educational interventions to improve inhaler technique are effective on the short-term. Periodical intervention reinforcement and longer follow-up studies, including clinical relevant endpoints and cost-effectiveness, are recommended.

  11. Oxidative stress in a rat model of cotton smoke inhalation-induced ...

    African Journals Online (AJOL)

    Background: Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model. Materials and Methods: ...

  12. Real-life characteristics of asthma inhaler device use in South Korea

    NARCIS (Netherlands)

    Wan Yau Ming, S.; Rhee, C.K.; Park, H.Y.; Yoo, K.H.; Kim, D.K.; Van Boven, J.F.; Price, D.; Park, H.S.

    2016-01-01

    Background and Aims: Historically, dry powder inhalers (DPIs) were considered to provide better airway distribution, easier identification of empty devices, and easier handling when compared to pressurized metered dose inhalers (pMDIs). Prior research into the major handling errors with inhaler

  13. Adequacy of inhaler technique used by people with asthma or chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Bang C

    2013-09-01

    Full Text Available INTRODUCTION: Asthma and chronic obstructive pulmonary disease (COPD are ongoing concerns to the health system. Poor inhaler technique results in less than optimal delivery of medicine to the lungs and consequent inadequate symptom control. AIM: This study aimed to assess inhaler technique amongst people with asthma and/or COPD. The secondary aims were to investigate who provided education on inhaler technique and whether age, gender or ethnicity was associated with poor inhaler technique. METHODS: People with asthma or COPD who presented to a community pharmacy with a prescription for a respiratory inhaler were invited to participate in the study. Participants completed a brief questionnaire and had their inhaler technique assessed against a standard checklist. RESULTS: There were 103 participants from 26 pharmacies, 86 with asthma and 17 with COPD. Just over half (52.5% of the assessments indicated good inhaler technique, with 68% of people using the Turbuhaler having good technique compared to 53% for the pressurised metered dose inhaler (pMDI with spacer and 47% for the pMDI alone. The majority of people (76% received their initial inhaler technique instruction from their doctor. Over half of participants did not recall having their inhaler technique rechecked. DISCUSSION: After prescribing appropriate therapy, correct inhaler technique is a cornerstone of achieving adequate therapy. Rechecking inhaler technique is a gap in care that needs to be addressed from an interdisciplinary perspective.

  14. Acute inhalation toxicity of carbonyl sulfide

    Energy Technology Data Exchange (ETDEWEB)

    Benson, J.M.; Hahn, F.F.; Barr, E.B. [and others

    1995-12-01

    Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).

  15. Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo.

    Science.gov (United States)

    Balbi, Matilde; Koide, Masayo; Wellman, George C; Plesnila, Nikolaus

    2017-11-01

    Subarachnoid hemorrhage (SAH) induces acute changes in the cerebral microcirculation. Recent findings ex vivo suggest neurovascular coupling (NVC), the process that increases cerebral blood flow upon neuronal activity, is also impaired after SAH. The aim of the current study was to investigate whether this occurs also in vivo. C57BL/6 mice were subjected to either sham surgery or SAH by filament perforation. Twenty-four hours later NVC was tested by forepaw stimulation and CO2 reactivity by inhalation of 10% CO2. Vessel diameter was assessed in vivo by two-photon microscopy. NVC was also investigated ex vivo using brain slices. Cerebral arterioles of sham-operated mice dilated to 130% of baseline upon CO2 inhalation or forepaw stimulation and cerebral blood flow (CBF) increased. Following SAH, however, CO2 reactivity was completely lost and the majority of cerebral arterioles showed paradoxical constriction in vivo and ex vivo resulting in a reduced CBF response. As previous results showed intact NVC 3 h after SAH, the current findings indicate that impairment of NVC after cerebral hemorrhage occurs secondarily and is progressive. Since neuronal activity-induced vasoconstriction (inverse NVC) is likely to further aggravate SAH-induced cerebral ischemia and subsequent brain damage, inverse NVC may represent a novel therapeutic target after SAH.

  16. Uso do óxido nítrico em pediatria Inhaled nitric oxide in pediatrics

    Directory of Open Access Journals (Sweden)

    José R. Fioretto

    2003-11-01

    Full Text Available OBJETIVO: Rever a literatura sobre óxido nítrico inalatório e descrever suas principais indicações clínicas em pediatria. FONTES DOS DADOS: Revisão bibliográfica e seleção de publicações mais relevantes sobre óxido nítrico inalatório, utilizando a base de dados Medline (últimos dez anos e a base de dados Cochrane de revisões sistemáticas. SÍNTESE DOS DADOS: A revisão incluiu os seguintes tópicos: introdução; metabolismo e efeitos biológicos; aplicações clínicas; dose, administração e retirada do gás; precações e efeitos adversos e contra-indicações. Quanto às aplicações clínicas, foram descritos o uso de óxido nítrico em hipertensão pulmonar persistente e insuficiência respiratória de recém-nascidos, síndrome do desconforto respiratório agudo, hipertensão pulmonar primária, cirurgia cardíaca, doença pulmonar obstrutiva crônica, anemia falciforme e broncoespasmo. CONCLUSÕES: O óxido nítrico inalatório é um tratamento com amplas possibilidades de utilização em clínica pediátrica. Seu uso é seguro em ambiente de terapia intensiva sob monitorização rigorosa. Como vasodilatador pulmonar seletivo, o óxido nítrico tem efeitos benéficos sobre as trocas gasosas e ventilação. Estudos controlados que enfoquem a administração precoce do gás são necessários em muitas condições, principalmente na síndrome do desconforto respiratório agudo.OBJECTIVE: To review the literature on inhaled nitric oxide and to describe its main clinical applications in pediatrics. SOURCES OF DATA: A 10 year literature review with selection of the most important publications on inhaled nitric oxide, using the Medline and Cochrane Systematic Review databases. SUMMARY OF THE FINDINGS: This review was organized as follows: introduction; metabolism and biological effects; clinical applications; dosage, gas administration and weaning; precautions and side-effects. Inhaled nitric oxide use was described in

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

    Directory of Open Access Journals (Sweden)

    Darbà J

    2015-10-01

    Full Text Available Josep Darbà,1 Gabriela Ramírez,2 Antoni Sicras,3 Pablo Francoli,4 Saku Torvinen,5 Rainel Sánchez-de la Rosa4 1Department of Economics, Universitat de Barcelona, 2BCN Health Economics and Outcomes Research SL, 3Dirección de Planificación, Badalona Serveis Assistencials, SA, Barcelona, 4Medical Department, TEVA Pharmaceutical, Madrid, Spain; 5Market Access Department, TEVA Pharmaceutical Europe BV, Amsterdam, the Netherlands Objective: This study aims to identify factors associated with poor adherence to COPD treatment in patients receiving a fixed-dose combination (FDC of inhaled corticosteroids and long-acting β2-agonist (ICS/LABA, focusing on the importance of inhaler devices.Methods: We conducted a retrospective and multicenter study based on a review of medical registries between 2007 and 2012 of COPD patients (n=1,263 treated with ICS/LABA FDC, whose medical devices were either dry powder inhalers (DPIs or pressurized metered-dose inhalers (pMDI. Medication adherence included persistence outcomes through 18 months and medication possession ratios. Data on exacerbations, comorbidities, demographic characteristics, and health care resource utilization were also included as confounders of adherence.Results: The analyses revealed that COPD patients whose medication was delivered through a DPI were less likely to have medication adherence compared to patients with pMDI, after adjusting for confounding factors, especially active ingredients. Younger groups of patients were less likely to be adherent compared to the oldest group. Smoker men were less likely to be adherent compared to women and non-smokers. Comorbidities decreased the probability of treatment adherence. Those patients that visited their doctor once a month were more likely to adhere to their medication regimen; however, suboptimal adherence was more likely to occur among those patients who visited more than three times per month their doctor. We also found that worsening of

  18. Second gas effect of N2O on oxygen uptake.

    Science.gov (United States)

    Nishikawa, K; Kunimoto, F; Isa, Y; Miyoshi, S; Takahashi, K; Morita, T; Arii, H; Goto, F

    2000-06-01

    The concept of the second gas effect is well known, however, there have been no studies that showed the relationship between alveolar oxygen concentration and arterial oxygen tension (PaO2) after the inhalation of nitrous oxide (N2O) in humans. The purpose of this study was to examine the changes in both end-tidal oxygen fraction (F(ET)O2) and PaO2 after N2O inhalation in patients under general anesthesia. Fifteen patients scheduled for elective orthopedic surgery were enrolled in this study. Anesthesia was maintained with the continuous infusion of propofol and with nitrogen (N2) and oxygen (O2) (6 L x min(-1), F1O2, 0.33). In all patients, the lungs were ventilated with a Servo 900C ventilator equipped with a gas mixer for O2, N2O, and N2. After obtaining baseline data, N2 was replaced with N2O maintaining FIO2 constant at 0.33. The changes in fractional concentration of O2, N2O, and N2 were continuously measured using mass spectrometer in a breath-by-breath basis. PaO2 and hemodynamic data were obtained at 1, 5, 10, 30 and 60 min after the start of N2O inhalation. Five minutes after N2O inhalation, F(ET)O2 increased from 0.27+/-0.01 to 0.31+/-0.02 (P<0.01) and PaO2 increased from 172.0+/-22.5 mm Hg to 201.0+/-10.3 mm Hg (P<0.01). These effects produced by N2O were observed for 30 min. These results confirm the concept of second gas effect of N2O on oxygen uptake in humans and provide evidence that the PaO2 increase correlated with the increase in F(ET)O2 after N2O inhalation.

  19. Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

    Science.gov (United States)

    2014-01-01

    Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post

  20. Effect of petroleum products inhalation on some haematological ...

    African Journals Online (AJOL)

    Haematotoxic implications of exposure to petroleum fumes through inhalation in human subjects were investigated. A total of 400 subjects (200 males and 200 females) aged between 18-30 years participated. Each gender was further categorized into two groups of 100 each for control and test, respectively. The test group ...

  1. Nitric oxide inhalation in infants with respiratory distress syndrome.

    Science.gov (United States)

    Skimming, J W; Bender, K A; Hutchison, A A; Drummond, W H

    1997-02-01

    This study was designed to test the hypothesis that nitric oxide inhalation increases systemic arterial blood oxygen tension of prematurely delivered infants with respiratory distress syndrome. Nitric oxide was administered to 23 preterm infants with a diagnosis of respiratory distress syndrome. The infants were randomly assigned to receive either 5 or 20 ppm of nitric oxide and were studied between 24 and 168 hours after delivery. The treatment period for each infant lasted 15 minutes and was preceded by and followed by a 15-minute control period. We evaluated all outcome variables by using two-way repeated measures analysis of variance; p values less than 0.01 were considered significant. Nitric oxide inhalation caused significant increases in the following: arterial blood oxygen tension, directly measured arterial oxyhemoglobin saturation, and transcutaneously measured arterial oxyhemoglobin saturation. No differences between the effects of the two nitric oxide concentrations were detected, nor were residual effects detected 15 minutes after either dose of nitric oxide was discontinued. Inhalation of both 5 and 20 ppm nitric oxide causes concentration-independent increases in the blood oxygen tensions of preterm infants with respiratory distress syndrome. We speculate that nitric oxide inhalation may be a useful adjunctive therapy for these patients.

  2. Cardiotoxicity induced by inhalation of petroleum products | Azeez ...

    African Journals Online (AJOL)

    Exposure to petroleum products has been associated with high blood pressure. This study was designed to investigate the effect of petroleum products on cardiac tissue architecture and creatine kinase (CK- MB). Forty male Sprague Dawley rats were exposed to diesel, kerosene and petrol by inhalation for eight weeks.

  3. Effects of inhaled nitric oxide on oxygenation and haemodynamic ...

    African Journals Online (AJOL)

    always mandatory for such procedures, it improves access to the operative field and expedites the surgery. The most is the endothelial dependent vasorelaxing factor nitric oxide. (NO). in theory inhaled nitric oxide (iNO) could increase oxygenation by selectively decreasing pulmonary resistance and increasing blood flow to ...

  4. Therapeutic effects of co-inhaled roflumilast or formoterol and ...

    African Journals Online (AJOL)

    Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice. Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated ...

  5. Inhalation Injury in Burns Patients in Ibadan | Adigun | Nigerian ...

    African Journals Online (AJOL)

    Conclusion: Reasons for the high mortality included lack of facilities for monitoring blood gasses as well as for ventilatory support and delays in early skin coverage. A high index of suspicion and knowledge of the appropriate management of inhalation injury are important for a good outcome. (Nig J Surg Res 2001; 3: 50 ...

  6. A Spreading Concern: Inhalational Health Effects of Mold

    National Research Council Canada - National Science Library

    Bob Weinhold

    2007-01-01

    .... As recently as 25 years ago, inhaled Effects of mold was considered primarily a nuisance, not a serious health threat. But the growing scientific and medical evidence suggests the threat is widespread and, for some people, quite serious. In the 9 June 2006 report Mold Prevention Strategies and Possible Health Effects in the Aftermath of Hurricanes and ...

  7. Dry powder inhalers under the microscope | Onyechi | Journal of ...

    African Journals Online (AJOL)

    Three major factors have driven the change, the need to eliminate the use of ozone layer depleting chlorofluorocarbon propellant systems employed in the formulation of metered dose inhalers (MDIs); the wider application of DPIs beyond asthma therapy to include local delivery of mucolytics, antibiotics, antitubercular and ...

  8. Therapeutic effects of co-inhaled roflumilast or formoterol and ...

    African Journals Online (AJOL)

    1056. 14. Vanacker N, Palmans E, Pauwels R, Kips J. Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats. Eur Respir J 2002; 20: 873-879. 15. Price D, Hillyer EV. Fluticasone propionate/formoterol fumarate in ...

  9. Serum specific IgE responses to inhalant allergens sensitization

    Directory of Open Access Journals (Sweden)

    Iris Rengganis

    2017-11-01

    Full Text Available Background: Serum specific immunoglobulin E (ssIgE sensitization to common inhalant allergens has not been studied in Indonesia. This study aimed to evaluate specific IgE production of common inhalant allergens in patients with asthma and/or allergic rhinitis in Jakarta, Indonesia.Methods: This was a cross-sectional study in adult patients with respiratory allergy from September to December 2016 at Cipto Mangunkusumo Hospital, Jakarta. Patients were included if they showed at least one positive skin prick test (SPT to environmental allergens. Serum specific IgE was assayed by using multiple allergosorbent methods. Inhalant allergens tested were dust mites, pollen, cockroach, animal dander, and mould. Serum IgE level more than 0.35 kU/L was considered positive.Results: One hundred subjects were enrolled (76% women. Dust mites made up 75% of sensitization, followed by cat/dog (31%, cockroach (27%, pollen (24%, and mould (6%. Almost all patients sensitized to cockroach, pollen, cat/dog epithelia and mould were also co-sensitized with dust mites. Twenty two percent of patients were negative to all tested allergens.Conclusion: IgE-sensitization to inhalant allergens varies widely in respiratory allergic patients. House dust and storage mites are the most common allergens. About one-fifth of the subjects did not show specific-IgE sensitization. Thus, this test should always be combined with SPT to diagnose allergy.

  10. Management of Inhaled Foreign Body and other Paediatric Airway ...

    African Journals Online (AJOL)

    Adults do get Upper Airway Obstruction from a variety of causes but the most frequently encountered patient with this condition is a baby or child, sometimes with respiratory failure in extremis, who has inhaled a maize seed, bean or peanut. Invariably there is an anxious parent present who has high expectations of a ...

  11. Characteristics of peaks of inhalation exposure to organic solvents

    NARCIS (Netherlands)

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

    2004-01-01

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

  12. Infant with Altered Consciousness after Cannabis Passive Inhalation

    Science.gov (United States)

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

    2012-01-01

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

  13. Adrenal function in asthmatic children treated with inhaled budesonide

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Damkjaer Nielsen, M

    1991-01-01

    The effect of the inhaled topical steroid budesonide on adrenal function was evaluated in 33 children (aged 7-15 years) with moderate bronchial asthma. The trial was designed as a prospective single-blind study of the effect of budesonide in daily doses of 200 microgram through 400 microgram to 8...

  14. Inhale while Dreaming: Human Exposure to Pollutants while Sleeping

    DEFF Research Database (Denmark)

    Corsi, Richard; Spilak, Michal; Boor, E., Brandon

    2012-01-01

    to the importance of this topic and to summarize past research. This will be followed by a series of three 8 minute presentations related to recent and on-going novel research related to emissions from mattresses, inhalation exposures, and position-specific intake fractions. One hour will be provided for audience...

  15. Inhaled Antibiotics for Gram-Negative Respiratory Infections

    Science.gov (United States)

    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

  16. Cellular targets of inhalational anaesthetic- and opioid receptor ...

    African Journals Online (AJOL)

    Several anaesthetics and anaesthetic adjuvants have been shown to limit the extent of myocardial injury due to ischaemia and reperfusion, a protective phenomenon known as anaesthetic-induced cardioprotection. Inhalational anaesthetics and opioid receptor agonists are among the key players in anaesthetic-induced ...

  17. Pathways of inhalation exposure to manganese in children ...

    Science.gov (United States)

    Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can occur from various sources and routes. Structural equation modeling was used to examine routes of exposure to Mn among children residing near a ferromanganese refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was hypothesized. Data for model evaluation were obtained from participants in the Communities Actively Researching Exposure Study (CARES). These data were collected in 2009 and included levels of Mn in residential soil and dust, levels of Mn in children's hair, information on the amount of time the child spent outside, heat and air conditioning in the home and level of parent education. Hair Mn concentration was the primary endogenous variable used to assess the theoretical inhalation exposure pathways. The model indicated that household dust Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn concentration (0.26), time children spent outside (0.24) and soil Mn (0.24) significantly contributed to the amount of Mn in household dust. These results provide a potential framework for understanding the inhalation exposure pathway for children exposed to ambient air Mn who live in proximity to an industrial emission source. The purpose of this study was to use a structural equations modeling approach combined with exposure estimates derived from air-dispersion modeling to assess potential inhalation exposure pathways for children to a

  18. Dimethylsulfoxide with heparin in the treatment of smoke inhalation injury.

    Science.gov (United States)

    Brown, M; Desai, M; Traber, L D; Herndon, D N; Traber, D L

    1988-01-01

    Recent studies suggest that lung lesions occurring in inhalation injury result from actions of oxygen-free radicals released from polymorphonuclear leukocytes marginating in the pulmonary microcirculation and tracheobronchial region. Peroxide and hydroxyl ions have been implicated as mediators in the increased microvascular permeability and pulmonary edema noted after inhalation injury. In this study we evaluated the use of an O2-free radical scavenger, dimethylsulfoxide (DMSO), and heparin in the treatment of smoke inhalation. Ewes (N = 26) that had been surgically prepared five days earlier were insufflated with smoke from burning cotton. There were four groups: controls (n = 7), DMSO (n = 6), heparin (n = 6), and DMSO plus heparin (n = 7). All animals were given ventilatory support to maintain their PO2 above 60 mmHg and their PCO2 below 45 mmHg. There was a significant difference in survival rates between groups. By 72 hours all seven of the control group were dead. All animals in the DMSO plus heparin group survived, four of the DMSO group died, and two of the heparin group died. Lung lymph flow was not as high in the DMSO plus heparin group as in the heparin-only group. DMSO was proved effective in reducing the lung injury associated with smoke inhalation.

  19. Improving the Efficiency of Inhalation Therapy in Young Children

    NARCIS (Netherlands)

    J.E. Festen

    2006-01-01

    textabstractInhalation therapy is the customary method to deliver medication to patients with lung disease. It is very difficult to deliver aerosolized drugs to the lungs efficiently and in a reproducible manner, especially in young children. Chapter 1 of this thesis deals with the background of

  20. Effects of Radon inhalation on physiology and disorders

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-12-31

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