TY  - JOUR
AU  - Farnoud, A.
AU  - Orak, S.
AU  - Schmid, O.
C1  - 56365
C2  - 47028
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - A9-A9
TI  - Numerical models of respiratory drug deposition and pharmacokinetics: Application to liposomal ciclosporin a (L-CSA).
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 32
IS  - 3
PB  - Mary Ann Liebert, Inc
PY  - 2019
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Orak, S.
AU  - Rothen-Rutishauser, B.*
AU  - Jud, C.*
AU  - Farnoud, A.
AU  - Bucholski, A.*
AU  - Egle, R.*
AU  - Boerner, G.*
AU  - Denk, O.*
AU  - Schmid, O.
C1  - 56368
C2  - 47020
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - A7-A7
TI  - Towards prediction of the pharmacokinetics of inhaled nanomedicine from physiological cell models: A case study with liposomal ciclosporin A (L-CSA) using the vitrocell cloud system.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 32
IS  - 3
PB  - Mary Ann Liebert, Inc
PY  - 2019
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Schmid, O.
C1  - 56367
C2  - 47026
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - A4-A4
TI  - Advanced in vitro and in silico models improve predictions of in vivo/clinical pharmacokinetics of nanocarrier-laden inhaled drugs.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 32
IS  - 3
PB  - Mary Ann Liebert, Inc
PY  - 2019
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Yang, L.
AU  - Gradl, R.*
AU  - Feuchtinger, A.
AU  - Morgan, K.S.*
AU  - Kutschke, D.
AU  - Stöger, T.
AU  - Razansky, D.
AU  - Walch, A.K.
AU  - Pfeiffer, F.*
AU  - Schmidt, O.
C1  - 56366
C2  - 47027
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - A12-A12
TI  - Novel imaging tolls for deciphering pulmonary aerosol deposition with single-cell resolution in non-dissected murine lungs.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 32
IS  - 3
PB  - Mary Ann Liebert, Inc
PY  - 2019
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Schmid, O.
C1  - 55676
C2  - 46435
CY  - 140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
SP  - 119-119
TI  - In Memoriam: Dr. Winfried Moller.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 31
IS  - 2
PB  - Mary Ann Liebert, Inc
PY  - 2018
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Background: Inhalation of aerosolized drugs is a promising route for noninvasive targeted drug delivery to the lung. Nanocarrier systems such as liposomes have been explored for inhalation therapy opening new avenues, including stabilization of nonsoluble drugs (e.g., Ciclosporin A [CsA]) and controlled release. Methods: The biokinetic behavior of the immunosuppressive drug CsA encapsulated in liposomes (L-CsA) at the lung epithelial barrier was studied in vitro. Human lung epithelial cells (alveolar A549 and bronchial 16HBE14o- epithelial cells) were exposed to aerosolized L-CsA at the air-liquid interface (ALI) using a dose-controlled air-liquid interface cell exposure (ALICE) system and the temporal profile of the L-CsA dose in the apical, basal, and cell compartment was monitored up to 24 hours. Results: Aerosolization of different volumes of L-CsA solution with the ALICE resulted in dose-controlled, spatially uniform, and reproducible L-CsA delivery. Cell viability at 24 hours postexposure was not impaired and immunofluorescence staining revealed the typical epithelial cell morphology in control as well as in L-CsA-exposed cells. The (pro-)inflammatory interleukin-8 levels were not elevated under any condition. The biokinetic analysis revealed that both cell types formed a tight, but imperfect, barrier for L-CsA resulting in initially high transbarrier L-CsA transport rates, which ceased after about 4 hours. Although substantial transbarrier L-CsA transport was observed for both cell types, respectively, a 150-fold higher L-CsA concentration was established in the apical and cell compared to the basal compartment. Most importantly, for pulmonary drug targeting, a high cellular L-CsA dose level (20%-25% of the delivered dose) was obtained rapidly (<1 hour) and maintained for at least 24 hours. Conclusions: The ALICE system combined with lung epithelial cells cultured at the ALI offers a reliable and relevant in vitro platform technology to study the effects of inhalable substances such as L-CsA under biomimetic conditions.
AU  - Schmid, O.
AU  - Jud, C.*
AU  - Umehara, Y.*
AU  - Mueller, D.*
AU  - Bucholski, A.*
AU  - Gruber, F.*
AU  - Denk, O.*
AU  - Egle, R.*
AU  - Petri-Fink, A.*
AU  - Rothen-Rutishauser, B.M.*
C1  - 52605
C2  - 44131
CY  - New Rochelle
SP  - 411-424
TI  - Biokinetics of aerosolized liposomal ciclosporin A in human lung cells in vitro using an air-liquid cell interface exposure system.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 30
IS  - 6
PB  - Mary Ann Liebert, Inc
PY  - 2017
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.
AU  - Darquenne, C.*
AU  - Fleming, J.S.*
AU  - Katz, I.*
AU  - Martin, A.R.*
AU  - Schroeter, J.*
AU  - Usmani, O.S.*
AU  - Venegas, J.*
AU  - Schmid, O.
C1  - 48553
C2  - 41175
CY  - New Rochelle
SP  - 107-126
TI  - Bridging the gap between science and clinical efficacy: Physiology, imaging, and modeling of aerosols in the lung.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 29
IS  - 2
PB  - Mary Ann Liebert, Inc
PY  - 2016
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Ferron, G.A.
AU  - Karg, E.W.
C1  - 47414
C2  - 40557
SP  - A38
TI  - Model of the hygroscopic particle deposition in the mouse lungs.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 28
IS  - 3
PY  - 2015
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Hofmann, W.*
AU  - Winkler-Heil, R.*
AU  - Möller, W.
AU  - Madl, P.*
AU  - Schmidt, O.
C1  - 47416
C2  - 40555
SP  - A43-A43
TI  - Modeling particle deposition in the mouse lung and extrapolation to the human lung.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 28
IS  - 3
PY  - 2015
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Karg, E.W.
AU  - Ferron, G.A.
AU  - Muelhopt, S.*
AU  - Paur, H.*
AU  - Zimmermann, R.*
C1  - 47419
C2  - 40527
SP  - A34
TI  - Is the deposited dose in an air-liquid-interface exposure system comparable to the human lungs?
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 28
IS  - 3
PY  - 2015
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
C1  - 47415
C2  - 40556
SP  - A29
TI  - Biokinetic accumulation of nanoparticles (NP) from lungs to secondary organs and tissues:Contribution of systemically translocated NP across the air-blood barrier versus mucociliary cleared, swallowed and aborbed NP across the gut walls.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 28
IS  - 3
PY  - 2015
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Möller, W.
AU  - Barapatre, N.
AU  - Hamm, J.*
AU  - Yildirim, A.Ö.
AU  - Stöger, T.
AU  - Srivastava, R.
AU  - Woerle, V.
AU  - Eickelberg, O.
AU  - Schmid, O.
C1  - 47417
C2  - 40554
SP  - A38
TI  - In vivo and ex vivo imaging of fluorescent markers in mouse lungs: Assessment of dose and 3D-distribution.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 28
IS  - 3
PY  - 2015
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Schittny, J.C.*
AU  - Barré, S.*
AU  - Haberthür, D.*
AU  - Semmler-Behnke, M.
AU  - Takenaka, S.
AU  - Kreyling, W.G.
AU  - Stampanoni, M.*
AU  - Tsuda, A.*
C1  - 47418
C2  - 40526
SP  - A40-A41
TI  - High resolution phase contrast imaging of sub-micron particles in unstained lung parenchyma.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 28
IS  - 3
PY  - 2015
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Lenz, A.-G.
AU  - Stöger, T.
AU  - Cei, D.
AU  - Schmidmeir, M.
AU  - Pfister, N.
AU  - Burgstaller, G.
AU  - Lentner, B.
AU  - Eickelberg, O.
AU  - Meiners, S.
AU  - Schmid, O.
C1  - 32178
C2  - 35309
CY  - New Rochelle
SP  - A16
TI  - Validation of the alice-cloud technology for functional efficacy studie with aerosolized drugs delivered to cells at the air-liquid interface.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 27
IS  - 4
PB  - Mary Ann Liebert, Inc
PY  - 2014
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Abstract Determination of the respiratory tract deposition of airborne particles is critical for risk assessment of air pollution, inhaled drug delivery, and understanding of respiratory disease. With the advent of nanotechnology, there has been an increasing interest in the measurement of pulmonary deposition of nanoparticles because of their unique properties in inhalation toxicology and medicine. Over the last century, around 50 studies have presented experimental data on lung deposition of nanoparticles (typical diameter≤100 nm, but here≤300 nm). These data show a considerable variability, partly due to differences in the applied methodologies. In this study, we review the experimental techniques for measuring respiratory tract deposition of nano-sized particles, analyze critical experimental design aspects causing measurement uncertainties, and suggest methodologies for future studies. It is shown that, although particle detection techniques have developed with time, the overall methodology in respiratory tract deposition experiments has not seen similar progress. Available experience from previous research has often not been incorporated, and some methodological design aspects that were overlooked in 30-70% of all studies may have biased the experimental data. This has contributed to a significant uncertainty on the absolute value of the lung deposition fraction of nanoparticles. We estimate the impact of the design aspects on obtained data, discuss solutions to minimize errors, and highlight gaps in the available experimental set of data.
AU  - Löndahl, J.*
AU  - Möller, W.
AU  - Pagels, J.H.*
AU  - Kreyling, W.G.
AU  - Swietlicki, E.*
AU  - Schmid, O.
C1  - 28154
C2  - 32969
CY  - New Rochelle
SP  - 229-254
TI  - Measurement techniques for respiratory tract deposition of airborne nanoparticles: A critical review.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 27
IS  - 4
PB  - Mary Ann Liebert
PY  - 2014
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Abstract Chronic rhinosinusitis (CRS) is the major disorder of the upper airways, affecting about 10-15% of the total population. Topical treatment regimens show only modest efficacy, because drug delivery to the posterior nose and paranasal sinuses is still a challenge. Therefore, there is a high rate of functional endoscopic sinus surgery in CRS patients. Most nasally administered aerosolized drugs, like nasal pump sprays, are efficiently filtered by the nasal valve and do not reach the posterior nasal cavity and the sinuses, which are poorly ventilated. However, as highlighted in this review, sinus ventilation and paranasal aerosol delivery can be achieved by using pulsating airflow, offering new topical treatment options for nasal disorders. Radioaerosol inhalation and imaging studies in nasal casts and in healthy volunteers have shown 4-6% of the nasally administered dose within the sinuses. In CRS patients, significant aerosol deposition in the sinus cavities was reported before sinus surgery. After surgery, deposition increased to the amount observed in healthy volunteers. In addition, compared with nasal pump sprays, retention kinetics of the radiolabel deposited in the nasal cavity was prolonged, both in healthy volunteers and in CRS patients. These efficiencies may be sufficient for topical aerosol therapies of sinus disorders and, due to the prolonged retention kinetics, may reduce application modes, but have to be proven in future clinical trials. Pulsating aerosols may offer additional new topical treatment options of nasal and sinus disorders before as well as after surgery.
AU  - Möller, W.
AU  - Schuschnig, U.*
AU  - Bartenstein, P.*
AU  - Meyer, G.*
AU  - Häussinger, K.*
AU  - Schmid, O.
AU  - Becker, S.*
C1  - 31860
C2  - 34827
CY  - New Rochelle
SP  - 255-263
TI  - Drug delivery to paranasal sinuses using pulsating aerosols.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 27
IS  - 4
PB  - Mary Ann Liebert, Inc
PY  - 2014
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Abstract Background: Rats are frequently used to study the pharmacological and toxicological effects of inhaled aerosol particles. The deposition behavior of aerosol particles in airways is affected by their hygroscopic properties, which accordingly influence the results of such studies. Method: A recently published nonhygroscopic aerosol particle deposition model for rat airways was extended with equations for hygroscopic particle growth in humid air and with a model to mimic the temperature and relative humidity conditions in the rat airways transformed from the upper human airways. As there are no experimental data available for hygroscopic deposition in rat lungs, several model assumptions were made for the humidity distribution in the upper rat airways. Results: The total and regional deposition probability of salt particles in the diameter range 0.02 to 5 μm in rat lung was significantly changed by the hygroscopic properties. The maximum ratios of the total deposition of inhaled initially dry sodium chloride, cobalt chloride, and zinc sulfate particles compared with nonhygroscopic particles were 3.28, 2.44, and 2.13, respectively, and the minimum ratios 0.57, 0.63, and 0.70, respectively. The corresponding maximum (and minimum) ratios for the hygroscopic drugs histamine dihydrochloride, carbenicillin disodium, and atropine sulfate were 1.86 (0.65), 1.53 (0.70), and 1.35 (0.76), respectively. Total deposition was about 20% higher in human airways than in rat airways. The flow regime in the rat upper airways influenced total and regional deposition much less than it did in human airways. Conclusion: The hygroscopicity of salt and drug aerosol particles is an important factor in rat lung deposition.
AU  - Ferron, G.A.
AU  - Upadhyay, S.
AU  - Zimmermann, R.
AU  - Karg, E.W.
C1  - 23731
C2  - 31261
SP  - 101-119
TI  - Model of the deposition of aerosol particles in the respiratory tract of the rat. II. Hygroscopic particle deposition.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 26
IS  - 2
PB  - Mary Ann Liebert
PY  - 2013
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Lenz, A.-G.
AU  - Schmidmeier, M.
AU  - Lentner, B.
AU  - Pfister, N.
AU  - Burgstaller, G.
AU  - Eickelberg, O.
AU  - Meiners, S.
AU  - Stöger, T.
AU  - Schmid, O.
C1  - 47030
C2  - 40483
SP  - A16-A17
TI  - Utilizing an efficient air-liquid interface cell exposure system (Alice) for in vitro efficacy testing of aerosolized liquid drugs.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 26
IS  - 2
PY  - 2013
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Möller, W.
AU  - Schuschnig, U.*
AU  - Saba, G.K.
AU  - Bartenstein, P.*
AU  - Haeussinger, K.*
AU  - Eickelberg, O.
AU  - Schmid, O.
AU  - Becker, S.*
C1  - 47026
C2  - 40487
SP  - A11-A11
TI  - Drug delivery to paranasal sinuses using pulsating aerosols.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 26
IS  - 2
PY  - 2013
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Möller, W.
AU  - Feng, S.*
AU  - Bartenstein, P.*
AU  - Haeussinger, K.*
AU  - Eickelberg, O.
AU  - Schmid, O.
AU  - Tatkov, S.*
C1  - 47027
C2  - 40486
SP  - A39-A40
TI  - Upper airway dead space clearance kinetics and efficiency during nasal high flow.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 26
IS  - 2
PY  - 2013
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Background: The pulmonary route is very promising for drug delivery by inhalation. In this regard, nanoparticulate drug delivery systems are discussed, and one very promising nano carrier example is gold nanoparticles (Au NP). Directly after their deposition, inhaled Au NP come into contact with pulmonary surfactant protein D (SP-D). SP-D can agglomerate Au NP in vitro, and this may influence the clearance as well as the systemic translocation in vivo. The aim of the present study was to investigate the clearance and translocation of Au NP at a very early time point after inhalation, as well as the influence of SP-D. Methods: Aerosolized 20-nm radioactively labeled Au NP were inhaled by healthy adult female mice. One group of mice received dissolved 10 μg of SP-D by intratracheal instillation prior to the Au NP inhalation. After a 2-hr Au NP inhalation period, the mice were killed immediately, and the clearance and translocation to the blood stream were investigated. Results: The highest amount of Au NP was associated with the lung tissue. In the bronchoalveolar lavage fluid (BALF), more Au NP remained free compared with the amount associated with the BALF cells. The amount of Au NP cleared by the mucociliary escalator was low, probably because of this very early time point. Instillation of SP-D prior to Au NP inhalation had no statistically significant effect on the biodistribution of the Au NP. Conclusion: Our data show that inhaled Au NP are retained in the mouse lungs and are translocated after a short time, and that SP-D has only a minor effect on Au NP translocation and clearance at a very early time point.
AU  - Schleh, C.
AU  - Holzwarth, U.*
AU  - Hirn, S.
AU  - Wenk, A.
AU  - Simonelli, F.*
AU  - Schäffler, M.
AU  - Möller, W.
AU  - Gibson, N.*
AU  - Kreyling, W.G.
C1  - 11581
C2  - 30699
SP  - 24-30
TI  - Biodistribution of inhaled gold nanoparticles in mice and the influence of surfactant protein D.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 26
IS  - 1
PB  - Mary Ann Liebert Inc.
PY  - 2013
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - BACKGROUND: Exhaled breath condensate (EBC) allows noninvasive monitoring of inflammation in the lung. Activation of inflammatory cells results in an increased production of reactive oxygen species, leading to the formation of hydrogen peroxide (H(2)O(2)). In addition, cigarette smoking causes an influx of inflammatory cells, and higher levels of H(2)O(2) have been found in EBC of smokers. However, there are still unresolved issues reflected by large variations in exhaled H(2)O(2) and uncertainties about the origin of H(2)O(2) release in the lung. METHODS: We collected EBC as fractionated samples from the airways and from the lung periphery in 10 nonsmokers, eight asymptomatic smokers, and in eight chronic obstructive pulmonary disease (COPD) patients, and H(2)O(2) concentration and acidity (pH) were analyzed in the airway and the alveolar fraction. RESULTS: In all subjects studied, H(2)O(2) was 2.6 times higher in the airway versus the alveolar fraction. Airway H(2)O(2) was twofold higher in smokers and fivefold higher in COPD patients compared to nonsmokers. In all study groups, there was no significant difference in deaerated pH between the airway and the alveolar sample. ONCLUSIONS: Exhaled H(2)O(2) is released at higher concentrations from the airways of all subjects studied, implying that the airways may be the dominant location of H(2)O(2) production. Because many lung diseases cause inflammation at different sites of the lung, fractionated sampling of EBC can reduce variability and maintain an anatomical allocation of the exhaled biomarkers.
AU  - Möller, W.
AU  - Heimbeck, I.
AU  - Weber, N.*
AU  - Saba, G.K.
AU  - Körner, B.*
AU  - Neiswirth, M.*
AU  - Kohlhäufl, M.*
C1  - 4815
C2  - 27573
SP  - 129-135
TI  - Fractionated exhaled breath condensate collection shows high hydrogen peroxide release in the airways.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 23
IS  - 3
PB  - Mary Ann Liebert Inc.
PY  - 2010
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - The dose of inhaled radiolabeled aerosols is usually assessed using gamma (GC) camera imaging. Because of the complex and inhomogeneous structure of the lung, consisting of soft tissue, the thoracic skeleton, blood vessels, and air spaces, proper attenuation correction coefficients are difficult to evaluate and the estimated doses bear high uncertainty. One hundred milliliters of aerosol boli composed of 100 nm diameter Tc-99m radiolabeled carbon particles (Technegas) were targeted either to the airways (AW) or to 800-mL volumetric lung depth (alveoli, AL) in 11 healthy volunteers. In addition, 750-mL full breaths (FB) of aerosol were inhaled to a 800-mL lung depth. The deposited dose was measured by collecting aerosol from inhaled and exhaled air stream on filters, which were analyzed for radioactivity. Lung imaging was performed using a planar GC (posterior). Ratios of GC counts to deposited dose (GC/DD) were similar after FB and AL administration, but twofold lower after AW administration (p < 0.01). Associated attenuation correction factors (ACF) were 2.5 +/- 0.5 (FB), 2.2 +/- 0.4 (AL), and 5.5 +/- 1.6 (AW, p < 0.01). Both GC/DD and ACF were highly correlated to the aerosol distribution index (central to peripheral ratio, C/P). After shallow bolus administration there was a negative correlation between body mass index and GC/DD. Inhalation of radioaerosols used in medical diagnosis and therapy in combination with high central airway deposition results in an underestimation of the deposited dose based on planar GC imaging. The aerosol distribution index C/P may provide one suitable indicator for corrections, which should be confirmed in future studies by individual attenuation analysis based on radiotracer transmission measurements.
AU  - Möller, W.
AU  - Felten, K.
AU  - Meyer, G.*
AU  - Meyer, P.
AU  - Seitz, J.*
AU  - Kreyling, W.G.
C1  - 1089
C2  - 26105
SP  - 45-54
TI  - Corrections in dose assessment of 99mTc radiolabeled aerosol particles targeted to central human airways using planar gamma camera imaging.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 22
IS  - 1
PB  - Mary Ann Liebert
PY  - 2009
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The data show that the asymmetry in shallow aerosol bolus deposition is primarily determined by lung ventilation. The reason for this asymmetry is unclear.
AU  - Möller, W.
AU  - Meyer, G.*
AU  - Scheuch, G.*
AU  - Kreyling, W.G.
AU  - Bennett, W.D.*
C1  - 2904
C2  - 26502
CY  - New Rochelle, NY
SP  - 333-339
TI  - Left-to-right asymmetry of aerosol deposition after shallow bolus inhalation depends on lung ventilation.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 22
IS  - 4
PB  - Mary Ann Liebert, Inc.
PY  - 2009
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Rats are used to test the toxicological and pharmacological effects of aerosol particles on the organism. For estimates of the delivered aerosol dose, lung deposition models provide a valuable tool. Here a previously developed deposition model for nonhygroscopic and hygroscopic aerosol particles in the lungs of man (Ferron et al., J. Aerosol Sci. 1988, 19:611) is adapted to the rat by implementing a lung structure for the rat combined with empirical equations for particle deposition due to impaction/sedimentation in the extrathoracic region and in bifurcations. To account for the effect of body weight (BW) on the physiological parameters (lung size, respiration frequency) we present BW-scaling laws with an estimated accuracy of about 16%. The present model shows good agreement with the measured total deposition (per breath) and other models from the literature to within the variability of the experimental data (20% absolute). Our calculations show that the variability of the experimental data is consistent with the combined effects from realistic variations in particle properties (mainly density) and physiological parameters (mainly activity level). For the alveolar region, which is of particular significance for pharmacological and health studies, we show that although the activity level may change the deposited dose by up to a factor of 2.2 for particles between 0.05 and 2.0 microm in diameter, the alveolar dose is almost independent (to within 10%) of activity level for particles between 0.5 and 1 microm, which makes this size range advantageous for pharmacological and toxicological experiments. The present model allows estimates of the total and regional particle dose deposited in the lungs of rats, which are consistent with experimental data. The advantage of the present model is that hygroscopic growth can be included in the calculations.
AU  - Schmid, O.
AU  - Bolle, I.
AU  - Harder, V.
AU  - Karg, E.W.
AU  - Takenaka, S.
AU  - Schulz, S.
AU  - Ferron, G.A.
C1  - 3261
C2  - 25580
SP  - 291-307
TI  - Model for the deposition of aerosol particles in the respiratory tract of the rat. I. Nonhygroscopic particle deposition.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 21
IS  - 3
PB  - Liebert
PY  - 2008
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
AU  - Semmler-Behnke, M.
AU  - Möller, W.
C1  - 5146
C2  - 23876
SP  - 74-83
TI  - Ultrafine particle-lung interactions: Does size matter?
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 19
PY  - 2006
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Schulz, S.
AU  - Harder, V.
AU  - Ibald-Mulli, A.
AU  - Khandoga, A.*
AU  - Koenig, W.*
AU  - Krombach, F.*
AU  - Radykewicz, R.
AU  - Stampfl, A.
AU  - Thorand, B.
AU  - Peters, A.
C1  - 1855
C2  - 22580
SP  - 1-22
TI  - Cardiovascular effects of fine and ultrafine particles.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 18
PY  - 2005
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
AU  - Semmler, M.
AU  - Möller, W.
C1  - 4112
C2  - 21886
SP  - 140-152
TI  - Dosimetry and toxicology of ultrafine particles.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 17
PY  - 2004
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Brand, P.
AU  - Letzel, S.*
AU  - Buchta, M.*
AU  - Scheuch, G.*
AU  - Windorfer, K.*
AU  - Hilla, W.*
AU  - Smith, H.J.*
AU  - Kraus, T.*
C1  - 10121
C2  - 21258
SP  - 143-151
TI  - Can Aerosol-Derived Airway Morphometry Detect Early, Asymptomatical Lung Emphysema?
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 16
PY  - 2003
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Schulz, S.
AU  - Eder, G.
AU  - Heyder, J.
C1  - 10120
C2  - 21232
SP  - 255-262
TI  - Lung volume is a determinant of aerosol bolus dispersion. 
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 16
PY  - 2003
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Ibald-Mulli, A.
AU  - Wichmann, H.-E.
AU  - Kreyling, W.G.
AU  - Peters, A.
C1  - 10122
C2  - 20723
SP  - 189-201
TI  - Epidemiological Evidence on Health Effects of Ultrafine Particles.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 15
PY  - 2002
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Brand, P.
AU  - Beinert, T.
AU  - Frühmann, G.
AU  - Hillebrecht, A.
AU  - Heyder, J.
C1  - 19816
C2  - 12965
SP  - 165-176
TI  - Aerosol derived Airway Morphometry at Different Levels of Lung Inflation.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 6
PY  - 1993
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
C1  - 18384
C2  - 11581
SP  - 93-110
TI  - Interspecies Comparison of Lung Clearance of "Insoluble" Particles.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 3 (Suppl.1)
PY  - 1990
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - A critical review is presented of the available experimental data on regional aerosol deposition in man. The data agree well for nasal and extrathoracic deposition. For the fast and slow cleared components of thoracic deposition, however, agreement is less satisfactory. The different experimental techniques are critically evaluated, and possible reasons for the observed discrepancies are discussed. Additionally, a semi-empirical model is presented which takes this evaluation into account, and which enables regional deposition to be calculated as function of particle size and respiratory parameters without lengthy computer models. The proposed equations explain and eliminate some of the intra- and inter-individual scatter of the data, and some of the discrepancies between the data from different laboratories. Where these discrepancies could not be eliminated, an additional 'conservative' model for dose estimations is offered which takes account of the uncertainty inherent to the data. A summary of the model equations is given in the appendix.
AU  - Stahlhofen, W.
AU  - Rudolf, G.
AU  - James, A.C.
C1  - 18144
C2  - 11004
SP  - 285-308
TI  - Intercomparison of Experimental Regional Aerosol Deposition Data.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 2
IS  - 3
PY  - 1989
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Light scattering photometers in combination with monodisperse test aerosols permit continuous recording of the aerosol concentration close to the entrance of the respiratory tract during the whole course of a breathing cycle. Data of this kind together with simultaneous records of the respiratory volumes provide new possibilities in lung function tests. Different inhalation apparatuses based on light scattering have been developed in the last decades. They are classified according to their principle of operation. Requirements with respect to the aerosols are worked out and potential sources of error arising in inhalation photometry are analyzed on the base of experiments. A novel 2-Mode-Photometer is described which can be operated in the photometric or analog mode at aerosol concentrations above 100 particles per cm3 and in the counting mode below 10 particles per cm3. Its applicability for various kinds of aerosol inhalation studies is demonstrated. With this device total deposition on human subjects can be measured at very low number concentrations. Under certain assumptions it can be also used as a sizing instrument for aerosol particles in the respiratory flow immediately at the entrance of the respiratory tract.  
AU  - Gebhart, J.
AU  - Heigwer, G.
AU  - Heyder, J.
AU  - Roth, C.
AU  - Stahlhofen, W.
C1  - 17213
C2  - 10238
SP  - 89-112
TI  - The Use of Light Scatter Photometry in Aerosol Medicine.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 1
IS  - 2
PY  - 1988
SN  - 0894-2684
ER  - 

TY  - JOUR
AB  - Thoracic airway calibers were estimated in 15 healthy subjects from gravitational losses during respiratory pauses of particles inhaled as aerosol boluses to different volumetric depths in the respiratory tract. Intersubject variability of thoracic airway dimensions and particle deposition for controlled and spontaneous mouth-breathing were correlated by Spearman's rank correlation analysis. The correlations between deposition of particles in the diameter range 1 - 5 μm and aerosol derived lung morphology suggest that the intersubject variability of particle deposition is primarily due to morphological differences between individuals. They also confirm the current understanding of behavior in the human respiratory tract of particles larger than 1 μm in diameter: with increasing particle size, the site of deposition is shifted proximally in the lungs.  
AU  - Heyder, J.
AU  - Gebhart, J.
AU  - Scheuch, G.
C1  - 17408
C2  - 10093
SP  - 81-88
TI  - Influence of Human Lung Morphology on Particle Deposition.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
VL  - 1
IS  - 2
PY  - 1988
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
AU  - Eder, K.
AU  - Erbe, F.
AU  - Ferron, G.A.
AU  - Haider, B.
AU  - Karg, E.W.
AU  - Schumann, G.
AU  - Heyder, J.
C1  - 17340
C2  - 10120
TI  - Particle Deposition in the Canine Respiratory Tract.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
PY  - 1988
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
AU  - Ferron, G.A.
AU  - Haider, B.
AU  - Bailey, M.R.
AU  - Andre, S.
AU  - Batchelor, A.
AU  - Collier, C.G.
AU  - Drosselmeyer, E.
AU  - Foster, P.P.
AU  - Hodgson, A.
AU  - Masse, R.
AU  - Metivier, H.
AU  - Morgan, A.
AU  - Müller, H.-L.
AU  - Patrick, G.
AU  - Pearman, I.
AU  - Pickering, S.
AU  - Ramsden, D.
AU  - Stirling, C.
AU  - Talbot, R.J.
C1  - 17341
C2  - 10119
TI  - Interspecies Comparison of the Lung Clearance of Inhaled Monodisperse Cobalt Oxide: Particle Transport from the Lungs to the GI Tract.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
PY  - 1988
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Kreyling, W.G.
AU  - Ferron, G.A.
AU  - Haider, B.
AU  - Andre, S.
AU  - Bailey, M.R.
AU  - Batchelor, A.
AU  - Collier, C.G.
AU  - Drosselmeyer, E.
AU  - Foster, P.
AU  - Hodgson, A.
AU  - Masse, R.
AU  - Metivier, H.
AU  - Müller, H.-L.
AU  - Patrick, G.
AU  - Pearman, I.
AU  - Pickering, S.
AU  - Ramsden, D.
AU  - Stirling, C.
AU  - Talbot, R.J.
C1  - 17343
C2  - 10117
TI  - Interspecies Comparison of the Lung Clearance of Inhaled Monodisperse Cobalt Oxide: Translocation from the Lungs to Blood.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
PY  - 1988
SN  - 0894-2684
ER  - 

TY  - JOUR
AU  - Stahlhofen, W.
AU  - Scheuch, G.
C1  - 17265
C2  - 10152
TI  - CHARTING THE UPPER HUMAN AIRWAYS BY MEANS OF AEROSOL BOLUSES.
JO  - J. Aerosol Med. Pulm. Drug Deliv.
PY  - 1988
SN  - 0894-2684
ER  -