G Scheuch

Lafayette College, Easton, Pennsylvania, United States

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Publications (121)188.59 Total impact

  • R Siekmeier, T Hofmann, G Scheuch
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    ABSTRACT: Systemic antibiotic treatment is established for many pulmonary diseases, e.g., cystic fibrosis (CF), bronchiectasis and chronic obstructive pulmonary disease (COPD) where recurrent bacterial infections cause a progressive decline in lung function. In the last decades inhalative administration of antibiotics was introduced into clinical routine, especially tobramycin, colistin, and aztreonam for treatment of CF and bronchiectasis. Even though they are important in systemic treatment of these diseases due to their antimicrobial spectrum and anti-inflammatory and immunomodulatory properties, macrolides (e.g., azithromycin, clarithromycin, erythromycin, and telithromycin) up to now are not administered by inhalation. The number of in vitro aerosol studies and in vivo inhalation studies is also sparse. We analyzed publications on preparation and administration of macrolide aerosols available in PUBMED focusing on recent publications. Studies with solutions and dry powder aerosols were published. Publications investigating physicochemical properties of aerosols demonstrated that macrolide aerosols may serve for inhalation and will achieve sufficient lung deposition and that the bitter taste can be masked. In vivo studies in rats demonstrated high concentrations and areas under the curve sufficient for antimicrobial treatment in alveolar macrophages and epithelial lining fluid without lung toxicity. The obtained data demonstrate the feasibility of macrolide inhalation which should be further investigated.
    Advances in experimental medicine and biology 09/2014; · 1.83 Impact Factor
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    ABSTRACT: Interest in bioequivalence (BE) of inhaled drugs derives largely from the desire to offer generic substitutes to successful drug products. The complexity of aerosol dosage forms renders them difficult to mimic and raises questions regarding definitions of similarities and those properties that must be controlled to guarantee both the quality and the efficacy of the product. Despite a high level of enthusiasm to identify and control desirable properties there is no clear guidance, regulatory or scientific, for the variety of aerosol dosage forms, on practical measures of BE from which products can be developed. As more data on the pharmaceutical and clinical relevance of various techniques, as described in this review, become available, it is likely that a path to the demonstration of BE will become evident. In the meantime, debate on this topic will continue.
    Therapeutic delivery 03/2013; 4(3):343-67.
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    ABSTRACT: Computer modeling is used widely to predict inhaled aerosol deposition in the human lung based on definition of the input conditions describing the aerosol characteristics, the breathing pattern and the airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three dimensional imaging data provides an opportunity to address this unmet need. Radioactive aerosol was administered to each of 11 healthy male subjects on two occasions under carefully monitored input conditions. Input parameters varied were particle size, depth of breathing, carrier gas and posture. The aerosol distribution was measured by combined single photon emission computed tomography and X-ray computer tomography (SPECT/CT). Airway anatomy was determined by high resolution CT imaging. The distribution of deposition was determined by a combination of 2D and 3D analysis and described in terms of the percentage of inhaled aerosol deposited in sections of the respiratory tract and in both spatial and anatomical sub-divisions within each lung. The percentage deposition in the conducting airways was also assessed by 24 h clearance. A set of imaging data of aerosol deposition has been produced in which the input parameters of inhalation are well described. The parameters were varied in a controlled manner to allow the sensitivity of predictive models to different factors to be tested. An initial analysis of the data is presented which will act as a guide that other centers can use to compare their own methodology. This data is considered to be of great potential value to computer modelers of aerosol deposition in validating their models.
    Journal of Aerosol Science 01/2012; 52:1–17. · 2.69 Impact Factor
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    ABSTRACT: Lung mucociliary clearance is impaired in patients with chronic obstructive pulmonary disease (COPD). Treatment guidelines recommend that patients with COPD receive maintenance therapy with long-acting beta-agonists and anticholinergic agents. Twenty-four patients with mild to moderate COPD received formoterol (12 μg, twice daily from Turbuhaler® dry powder inhaler (DPI)) or tiotropium (18 μg, once daily from Handihaler® DPI) for 14 days. They also received single doses of formoterol, tiotropium, salbutamol (200 μg) and placebo. A radioaerosol technique was used to assess the effects on mucus clearance of 14 days treatment with formoterol or tiotropium, as well as single doses of these drugs. The 4 h whole lung retention of radioaerosol was significantly higher after 14 days treatment with tiotropium (P = 0.016), but not after 14 days treatment with formoterol. However, patients bronchodilated after 14 days treatment with both drugs, so that the deposited radioaerosol may have had an increased distance to travel in order to be cleared by mucociliary action. A single dose of formoterol enhanced radioaerosol clearance significantly compared to other single dose treatments (P < 0.05). Formoterol (12 μg) enhances mucus clearance in patients with mild to moderate COPD when given as a single dose, and may do so when given for 14 days. Studies of longer duration would be needed in order to assess the effects of the study drugs on mucus clearance when they are used for long-term maintenance therapy.
    Respiratory medicine 03/2011; 105(6):900-6. · 2.33 Impact Factor
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    Journal of Cystic Fibrosis - J CYST FIBROS. 01/2011; 10.
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    ABSTRACT: Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.
    Journal of Aerosol Medicine and Pulmonary Drug Delivery 12/2010; 23 Suppl 2:S39-57. · 2.89 Impact Factor
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    ABSTRACT: A workshop/symposium on “Mucociliary and Cough Clearance (MCC/CC) as a Biomarker for Therapeutic Development” was held on October 21–22, 2008, in Research Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they may be optimized for assessing new therapies designed to improve clearance of airway secretions from the lungs. The utility of MCC/CC as a biomarker for disease progression and therapeutic intervention is gaining increased recognition as a valuable tool in the clinical research community. A number of investigators currently active in using MCC/CC for diagnostic or therapeutic evaluation presented details of their methodologies. Attendees participating in the workshop discussions included those interested in the physiology of MCC/CC, some of who use in vitro or animal methods for its study, pharmaceutical companies developing muco-active therapies, and many who were interested in establishing the methods in their own clinical laboratory. This review article summarizes the presentations for the in vivo human MCC/CC methods and the discussions both at and subsequent to the workshop between the authors to move forward on a number of questions raised at the workshop.
    Journal of Aerosol Medicine and Pulmonary Drug Delivery 10/2010; 23(5):261-72. · 2.89 Impact Factor
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    ABSTRACT: Abnormalities in alveolar coagulation occur in idiopathic pulmonary fibrosis (IPF). Anticoagulants attenuate bleomycin-induced lung fibrosis in animals. In this study, we first examined the pharmacokinetics of inhaled heparin in healthy subjects. Second, we investigated the safety and tolerability of heparin inhalation in IPF patients. Coagulation assays were performed in blood and bronchoalveolar lavage fluid samples from 19 healthy volunteers after inhalation of increasing amounts of unfractionated heparin. The acute effects of heparin inhalation on lung function and exercise capacity and the safety and tolerability of chronic heparin inhalation for 28 days were assessed in 20 IPF patients in an open-label exploratory pilot study. In healthy subjects, inhalation of 150,000 IU heparin ("filled dose") significantly increased the partial thromboplastin time and anti-factor Xa activity in blood samples indicating the threshold dose. The local alveolar anticoagulant effect was detectable up to 72 h, and the alveolar half-life was estimated at 28 h. In IPF-patients, no acute deleterious effects on pulmonary function, gas exchange, or exercise capacity were noted after inhalation of the threshold dose. During chronic treatment, where one-fourth of the threshold dose was inhaled every 12 h for 28 days to obtain a steady-state anticoagulant activity in the alveolar space approximating the anticoagulant activity observed after threshold dose inhalation, no heparin-related side effects, such as hemoptysis or heparin-induced antibodies and thrombocytopenia, were detected in any patient, and median lung function values, exercise capacity, and quality of life scores appeared largely unaltered. Three adverse and one serious adverse events were noted; however, the relation of these events to the heparin inhalation was assessed as "unlikely" or "no relation" in each case. Inhaled heparin appears to be safe and well tolerated in IPF patients. Future clinical trials are required to demonstrate the long-term safety and efficacy of inhaled heparin in IPF.
    Journal of Aerosol Medicine and Pulmonary Drug Delivery 06/2010; 23(3):161-72. · 2.89 Impact Factor
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    ABSTRACT: Medical aerosols may be delivered in combination with gases other than air, thus it is of interest to assess the effects of gas properties on the characteristics of the administered aerosol separately from effects on ventilation distribution and particle deposition mechanisms. This work investigated the influence of the supplied gas, either air or a mixture containing 78% helium and 22% oxygen, on droplet sizes produced by a vibrating mesh nebulizer incorporated in a combined gas–aerosol delivery system. Droplet size distributions were measured by laser diffraction. Nebulization was performed using three different meshes, producing droplets with nominal volume median diameters (VMDs) of 3, 4, or 5 μm. Measured VMDs were stable, in that they were in all cases within ±10% of their nominal values, and unaffected by humidity or dilution of the aerosol stream. While VMDs were consistently 5–10% smaller in helium–oxygen than in air, this variation was small compared to the variation between meshes. Accordingly, unlike jet nebulizers, vibrating mesh nebulizers having high output rates can be operated in helium–oxygen with only minor impact on emitted droplet sizes. This will be attractive in the design of controlled clinical studies investigating aerosol delivery in helium–oxygen. In assessing such therapies, it is important to distinguish effects of gas properties on the characteristics of the administered aerosol from effects on particle and fluid mechanics influencing the regional distribution of aerosol in the lung. Use of an aerosol delivery device that is virtually unaffected by changing gas properties, such as that tested in the present study, is a straightforward way to make such a distinction.
    Journal of Aerosol Science. 01/2010;
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    ABSTRACT: In the treatment of pulmonary diseases the inhalation of aerosols plays a key role - it is the preferred route of drug delivery in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. But, in contrast to oral and intravenous administration drug delivery to the lungs is controlled by additional parameters. Beside its pharmacology the active agent is furthermore determined by its aerosol characteristics as particle diameter, particle density, hygroscopicity and electrical charge. The patient related factors like age and stage of pulmonary disease will be additionally affected by the individual breathing pattern and morphometry of the lower airways. A number of these parameters with essential impact on the pulmonary drug deposition can be influenced by the performance of the inhalation system. Therefore, the optimization of nebulisation technology was a major part of aerosol science in the last decade. At this time the control of inspiration volume and air flow as well as the administration of a defined aerosol bolus was in the main focus. Up to date a more efficient and a more targeted pulmonary drug deposition - e.g., in the alveoli - will be provided by novel devices which also allow shorter treatment times and a better reproducibility of the administered lung doses. By such means of precise dosing and drug targeting the efficacy of inhalation therapy can be upgraded, e.g., the continuous inhalation of budesonide in asthma. From a patients' perspective an optimized inhalation manoeuvre means less side effects, e.g., in cystic fibrosis therapy the reduced oropharyngeal tobramycin exposure causes fewer bronchial irritations. Respecting to shorter treatment times also, this result in an improved quality of life and compliance. For clinical trials the scaling down of dose variability in combination with enhanced pulmonary deposition reduces the number of patients to be included and the requirement of pharmaceutical compounds. This review summarises principles and advances of individualised controlled inhalation (ICI) as offered by the AKITA inhalation system.
    European journal of medical research 12/2009; 14 Suppl 4:71-7. · 1.10 Impact Factor
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    ABSTRACT: In the last three decades methods for recombinant synthesis of peptides and proteins were developed allowing the production of large amounts of these substances for clinical treatment (e.g. growth factors, hormones, monoclonal antibodies and cytokines) (Agu et al. 2001; Patton and Byron 2007). Because of their biochemical properties (high molecular weight, hydrophilia, sensitivity against chemicals and proteolytic enzymes) these compounds cannot be administered orally, but require parenteral administration resulting in negative effects on convenience and compliance of the patients in cases of chronic diseases (e.g. diabetes mellitus). Inhaled application (via nose or mouth) of high molecular weight compounds seems to be a method of choice. However, much better conditions for absorption are found in the lung periphery (i.e. the alveolar region) making the lung to an important target for inhalative administration of drugs with systemic mode of action. Firstly, the size of the alveolar surface is about the half of a tennis court depending on the distension of the lung and much larger than that of the nose (about 180 cm2) (Niven 1995; Wolff 1998). Another advantage is the thin alveolar epithelium. Its thickness in most regions is between 0.1 and 0.2 μm (Patton and Platz 1992) resulting in a total distance between epithelial surface and blood between 0.5 and 1.0 µm (Wolff 1998) which is much less than in the bronchial tract where the deposited substances have to pass a distance of 30–40 μm and more between mucus surface and blood (Wolff 1998, Patton and Byron 2007). Several preconditions must be fulfilled to allow administration of adequate and reproducible drug doses for treatment of systemic diseases by inhaled aerosols. These are biophysical and physiological factors (e.g. aerosol particle size, and breathing manoeuvre (inspired volume, inspiratory flow, endinspiratory breathhold time)) which are subject of other reviews (Patton and Byron 2007; Scheuch et al. 2006; Scheuch and Siekmeier 2007) as well as physical and biochemical stability of the pharmaceutical compounds designed for aerosolisation (aqueous solution, dry powder, suspension or solution in propellants (Niven 1995; Yu and Chien 1997).
    11/2009: pages 227-249;
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    R Siekmeier, G Scheuch
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    ABSTRACT: Clinical experience since many years has shown that aerosol inhalation is an established route for the treatment of pulmonary diseases. In contrast, treatment of systemic diseases by means of aerosol inhalation is a novel therapeutic approach. This was caused for a long time by a lack of accuracy, efficiency, and reproducibility of the administered drug doses due to a poor knowledge of the physiological background of aerosol inhalation, an insufficient inhaler technology as well as a suboptimal breathing procedure. However, these problems have been solved in the last years and nowadays modern aerosol delivery systems allow the production of an aerosol with a defined and optimised particle size combined with an optimized breathing maneuver and optimization of the efficacy of the technology. Clinical studies demonstrated that only a small number of morphological factors (e.g., exogen allergic alveolitis, active sarcoidosis, active smoking) influence alveolar drug deposition and the inhaled systematically active compounds caused no relevant allergic reactions even after inhalation for longer time periods. Up to now, most data are available for the inhalation of insulin which has been introduced in clinical treatment for a short time. However, a lot of other molecules have been tested in aerosol inhalation studies. This review describes some examples other than insulin in the field of inhalant treatment of systemic diseases.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 11/2009; 60 Suppl 5:15-26. · 2.48 Impact Factor
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    ABSTRACT: After shallow bolus inhalation of radiolabeled aerosols, gamma camera imaging has shown a left-right asymmetry, with a higher fraction of deposited particles in the left lung. It was not clear, however, whether this phenomenon was an effect of asymmetry in lung ventilation or aerosol deposition efficiency. Lung ventilation and aerosol deposition was studied after shallow bolus inhalation and gamma camera imaging in nine healthy nonsmokers and 10 asymptomatic smokers. A 100-mL (81m)Kr-gas boli were administered within the Fowler and within the phase-1 dead space, respectively. In addition, 1-L full breaths of 81m-Kr-gas were inhaled. For aerosol deposition subjects inhaled 100-mL boli of 100-nm diameter radiolabeled carbon particles with shallow and deep penetration. Left-to-right (L/R) and central-to-peripheral (C/P) activity distribution of the lung was analyzed. None of the parameters analyzed were significantly different between nonsmokers and smokers. The full-breath 81m-Kr-gas inhalation revealed a similar activity distribution over the left and right lungs, according to their respective volumes (L/R ratio = 0.84 +/- 0.04; mean +/- SE). In contrast, the shallow bolus inhalation of 81m-Kr-gas to the phase-1 dead space revealed more activity in the left lung (L/R ratio = 1.49 +/- 0.15, normalized to full-breath Kr-gas L/R). This same left-right asymmetry was observed for the aerosol after shallow bolus inhalation (L/R ratio = 1.69 +/- 0.15), and there was no significant difference between Kr-gas and aerosol L/R ratio. C/P activity ratios of bolus inhalation to the phase-1 dead space were 1.71 +/- 0.19 and 1.79 +/- 0.15 (normalized to full-breath Kr-gas C/P) for gas and aerosol, respectively, and correlated with the L/R ratios. The data show that the asymmetry in shallow aerosol bolus deposition is primarily determined by lung ventilation. The reason for this asymmetry is unclear.
    Journal of Aerosol Medicine and Pulmonary Drug Delivery 08/2009; 22(4):333-9. · 2.89 Impact Factor
  • Journal of Cystic Fibrosis - J CYST FIBROS. 01/2009; 8.
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    R Siekmeier, G Scheuch
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    ABSTRACT: Aerosol inhalation is an established route of medical administration for the treatment of pulmonary diseases. In contrast, aerosol inhalation for treatment of systemic diseases is a novel therapeutic approach. Clinical use of the latter therapy for many years has been limited by the lack of accuracy, efficiency, and reproducibility of the administered doses. Usually, only a small fraction of inhaled drug reached the target region within the lungs. Further problems were the risk of potential allergic reactions in the respiratory tract and a potential variability of drug absorption from the alveoli into the circulation. These problems have been solved in the last years by modern aerosol delivery systems allowing the production of an aerosol with a defined and optimised aerosol particle size combined with an optimized breathing maneuver and optimization of the efficacy of the technology. Furthermore, there were no observations of relevant allergic reactions after inhalation of systemically active drugs in numerous studies. Studies demonstrated that only a small number of morphological factors influence alveolar drug deposition (e.g., exogen allergic alveolitis, active sarcoidosis, active smoking). In consequence, an increasing number of studies investigated the systemic effect of inhaled high molecular weight substances (e.g., insulin, heparin, interleukin-2) and demonstrated that controlled aerosol therapy may serve as a non-invasive alternative for drug application by means of a syringe. Our review briefly summarizes the mechanisms for pulmonary absorption of macromolecules and gives an overview on prior research in the field of inhalant treatment of systemic diseases.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 6:53-79. · 2.48 Impact Factor
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    R Siekmeier, G Scheuch
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    ABSTRACT: After more than 80 years of history the American and European Drug Agencies (FDA and EMEA) approved the first pulmonary delivered version of insulin (Exubera) from Pfizer/Nektar early 2006. However, in October 2007, Pfizer announced it would be taking Exubera off the market, citing that the drug had failed to gain market acceptance. Since 1924 various attempts have been made to get away from injectable insulin. Three alternative delivery methods where always discussed: Delivery to the upper nasal airways or the deep lungs, and through the stomach. From these, the delivery through the deep lungs is the most promising, because the physiological barriers for the uptake are the smallest, the inspired aerosol is deposited on a large area and the absorption into the blood happens through the extremely thin alveolar membrane. However, there is concern about the long-term effects of inhaling a growth protein into the lungs. It was assumed that the large surface area over which the insulin is spread out would minimize negative effects. But recent news indicates that, at least in smokers, the bronchial tumour rate under inhaled insulin seems to be increased. These findings, despite the fact that they are not yet statistical significant and in no case found in a non-smoker, give additional arguments to stop marketing this approach. Several companies worked on providing inhalable insulin and the insulin powder inhalation system Exubera was the most advanced technology. Treatment has been approved for adults only and patients with pulmonary diseases (e.g., asthma, emphysema, COPD) and smokers (current smokers and individuals who recently quitted smoking) were excluded from this therapy. Pharmacokinetics and pharmacodynamics of Exubera are similar to those found with short-acting subcutaneous human insulin or insulin analogs. It is thus possible to use Exubera as a substitute for short-acting human insulin or insulin analogs. Typical side effects of inhaled insulin were coughing, shortness of breath, sore throat and dry mouth. Physical exercise increases the transport of inhaled insulin into the circulation and in consequence the likelihood of hypoglycemia. Other problems were the inability to deliver precise insulin doses, because the smallest blister pack available contained the equivalent of 3 U of regular insulin and this dose would make it difficult for many people using insulin to achieve accurate control, which is the real goal of any insulin therapy. For example, someone on 60 U of insulin per day would lower the blood glucose about 90 mg/dl (5 mmol) per 3 U pack, while someone on 30 U a day would drop 180 mg/dl (10 mmol) per pack. Precise control was not possible, especially compared with an insulin pump that can deliver one twentieth of a unit with precision. Another disadvantage was the size of the device. The Exubera inhaler, when closed, was about the size of a 200 ml water glass. It opened to about twice the size for delivery. To our information also other companies (Eli Lilly in cooperation with ALKERMES, Novo Nordisk (AERx, Liquid), Andaris (Powder)) stopped further development and it is unclear whether an inhaled form of insulin will ever be marketed, because of the problems that have occurred. Only Mannkind (Technosphere, Powder) is still working on a Phase III trial. However, our review will briefly summarize the experience regarding inhalant administration of insulin and will describe potential future developments for this type of therapy focussing on the lung.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 01/2009; 59 Suppl 6:81-113. · 2.48 Impact Factor
  • R Siekmeier, G Scheuch
    Pneumologie 01/2009; 63(02).
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    ABSTRACT: The aim of this study was to determine particle clearance and retention from non-alveolated airways of 14 healthy subjects (HS), 10 subjects with asymptomatic bronchial hyperresponsiveness (BHR), and 23 patients with chronic obstructive pulmonary disease (COPD). Monodisperse iron oxide particles of 1.6 micro m geometric and 3.5 micro m aerodynamic diameter labeled with (99m)Tc were delivered to the airways by inspiration of small aerosol boli into shallow volumetric lung depths. In each subject the penetration front depth of the aerosol boli was adjusted to 55% of the Fowler dead space of the airways. Particle deposition was enhanced by about 7 seconds of breath-holding after bolus inhalation. Retention of the particles in the airways during the 48 hours after their administration was assessed by measuring the decline in lung activity with a sensitive gamma counter. Particle deposition was not significantly different among study groups. Twenty-four hour particle retention in the airways was not different among study groups. Sixty-one percent of the particles were retained at 24 hours in HS, 58% in BHR, and 64% in COPD. However, subjects with BHR showed accelerated mucociliary clearance compared to healthy subjects, whereas clearance was retarded in COPD patients. This long-term particle retention in the airways has to be taken into account in aerosol toxicology risk assessment and aerosol therapy dose evaluation.
    Experimental Lung Research 12/2008; 34(9):531-49. · 1.47 Impact Factor
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    ABSTRACT: Little is known about clearance of ultrafine carbon particles from the different regions of the human lung. These particles may accumulate and present a health hazard because of their high surface area. Technetium Tc 99m ((99m)Tc)-radiolabeled 100-nm-diameter carbon particles were inhaled by healthy nonsmokers, asymptomatic smokers, and by patients with chronic obstructive pulmonary disease (COPD). Using a bolus inhalation technique, particle deposition was targeted either to the airways or to the lung periphery, and retention, clearance, and translocation were measured using retained radiotracer imaging. In vitro studies revealed that mean leaching of soluble (99m)Tc-radiotracer from the carbon particles was 4.1 (2.6 [SD]) % after 24 hours. Cumulative (99m)Tc activity in urine at 24 hours was 1.1 (1.3) % of activity deposited in the lungs. In the lung periphery, particle retention was not affected by smoking or pulmonary disease; retention was 96 (3) % after 24 hours. The small amount of clearance could be attributed to leaching of the (99m)Tc label, suggesting negligible particle clearance. In healthy nonsmokers, retention of particles targeted to the airways was 89 (6) and 75 (10) % after 1.5 and 24 hours, respectively. Radiolabel activity did not accumulate in the liver. Within the limits of detection of our experimental system, most inhaled ultrafine carbon particles are retained in the lung periphery and in the conducting airways without substantial systemic translocation or accumulation in the liver at 48 hours. Repeated exposure may result in significant pulmonary accumulation of ultrafine particles.
    American Journal of Respiratory and Critical Care Medicine 03/2008; 177(4):426-32. · 11.04 Impact Factor
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    Lutz Heinemann, Gerhard Scheuch, Tim Heise
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    ABSTRACT: Inhalation of insulin is the first alternative route of insulin administration, which has been developed to such a mature status that the first product (Exubera, Pfizer) was made available to the market and subsequently withdrawn as of early 2008. In view of the relatively low bioavailability of inhaled insulin and the intraindividual variability of the metabolic effect induced (which is in the range of that of subcutaneously applied regular insulin), one wonders how to improve both aspects. Unfortunately, it appears as if the impact of the inhalation maneuver on insulin deposition in the deep lung has not been studied extensively. We present some thoughts and data from an alveolar model and propose an experimental procedure that might be helpful in the quantitative evaluation of the impact of the insulin inhalation maneuver.
    Journal of diabetes science and technology 03/2008; 2(2):297-9.

Publication Stats

1k Citations
188.59 Total Impact Points

Institutions

  • 2010
    • Lafayette College
      Easton, Pennsylvania, United States
  • 1998–2010
    • University of North Carolina at Chapel Hill
      • Center for Environmental Medicine, Asthma and Lung Biology
      North Carolina, United States
  • 2009
    • Bundesinstitut für Arzneimittel und Medizinprodukte
      Bonn, North Rhine-Westphalia, Germany
  • 1992–2008
    • Helmholtz Zentrum München
      München, Bavaria, Germany
  • 2005
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 2001
    • Robert Koch Institut
      Berlín, Berlin, Germany
  • 1999
    • Asklepios Fachkliniken München-Gauting
      München, Bavaria, Germany