42 results found
Biddiscombe MF, Usmani OS, 2021, Delivery and adherence with inhaled therapy in asthma, MINERVA MEDICA, Vol: 112, Pages: 564-572, ISSN: 0026-4806
Verbanck S, Biddiscombe MF, Usmani OS, 2020, Inhaled aerosol dose distribution between proximal bronchi and lung periphery, European Journal of Pharmaceutics and Biopharmaceutics, Vol: 152, Pages: 18-22, ISSN: 0939-6411
Modern inhaled drug discovery programs assess dose delivery to proximal and distal airways using rudimentary imaging indices, where relative deposition is estimated by generically defined 'central' and 'peripheral' lung regions. Utilizing recent data linking the proximal airway topology to a characteristic pattern of aerosol lung deposition, we provide a direct measure of dose distribution between the proximal bronchi and the distal lung. We analyzed scintigraphic lung images of twelve asthma patients following inhalation of 1.5-, 3- and 6-µm monodisperse drug particles at breathing flows of 30- and 60-L/min. We explicitly used the central hot-spots associated with each patient's specific bronchial topology to obtain a direct measure of aerosol deposition in the proximal bronchi, rather than applying standard templates of lung boundaries. Maximum deposition in the central bronchi (as % of lung deposition) was 52±10(SD)% (6µm;60L/min). Minimum central deposition was 17±2(SD)% (1.5µm;30L/min) where the 83% aerosol 'escaping' deposition in the central bronchi reached 75±17(SD)% of the lung area that could be reached by Krypton gas. For all particle sizes, hot-spots appeared in the same patient-specific central airway location, with greatest intensity at 60L/min. For a range of respirable aerosol sizes and breathing flows, we have quantified deposited dose in the proximal bronchi and their distal lung reach, constituting a platform to support therapeutic inhaled aerosol drug development.
Maher TM, Biddiscombe M, Fahy WA, et al., 2018, The Topical Study Of Inhaled Drug (salbutamol) Delivery In Idiopathic Pulmonary Fibrosis, Respiratory Research, Vol: 19, ISSN: 1465-9921
BackgroundOur aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF).MethodsThe TOPICAL study was a 4-period, partially-randomised, controlled, crossover study to investigate four aerosolised approaches in IPF subjects. Nine subjects were randomised to receive 99mTechnetium-labelled monodisperse salbutamol (1.5 μm or 6 μm; periods 1 and 2). Subjects also received radio-labelled salbutamol using a polydisperse nebuliser (period 3) and unlabelled salbutamol (400 μg) using a polydisperse pressurized metered dose inhaler with volumatic spacer (pMDI; period 4).ResultsSmall monodisperse particles (1.5 μm) achieved significantly better total lung deposition (TLD, mean % ± SD) than larger particles (6 μm), where polydisperse nebulisation was poor; (TLD, 64.93 ± 10.72; 50.46 ± 17.04; 8.19 ± 7.72, respectively). Small monodisperse particles (1.5 μm) achieved significantly better lung penetration (mean % ± SD) than larger particles (6 μm), and polydisperse nebulisation showed lung penetration similar to the small particles; PI (mean ± SD) 0.8 ± 0.16, 0.49 ± 0.21, and 0.73 ± 0.19, respectively. Higher dose-normalised plasma salbutamol levels were observed following monodisperse 1.5 μm and 6 μm particles, compared to polydisperse pMDI inhalation, while lowest plasma levels were observed following polydisperse nebulisation.ConclusionOur data is the first systematic investigation of inhaled drug delivery in fibrotic lung disease. We provide evidence that inhaled drugs can be optimised to reach the peripheral areas of the lung where active scarring occurs in IPF.
Verbanck S, Ghorbaniasl G, Biddiscombe MF, et al., 2016, Inhaled aerosol distribution in human airways: a scintigraphy-guided study in a 3D printed model, Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol: 29, Pages: 525-533, ISSN: 1941-2711
Background: While it is generally accepted that inertial impaction will lead to particle loss as aerosol is being carried into the pulmonary airways, most predictive aerosol deposition models adopt the hypothesis that the inhaled particles that remain airborne will distribute according to the gas flow distribution between airways downstream.Methods: Using a 3D printed cast of human airways, we quantified particle deposition and distribution and visualized their inhaled trajectory in the human lung. The human airway cast was exposed to 6 μm monodisperse, radiolabeled aerosol particles at distinct inhaled flow rates and imaged by scintigraphy in two perpendicular planes. In addition, we also imaged the distribution of aerosol beyond the airways into the five lung lobes. The experimental aerosol deposition patterns could be mimicked by computational fluid dynamic (CFD) simulation in the same 3D airway geometry.Results: It was shown that for particles with a diameter of 6 μm inhaled at flows up to 60 L/min, the aerosol distribution over both lungs and the individual five lung lobes roughly followed the corresponding distributions of gas flow. While aerosol deposition was greater in the main bronchi of the left versus right lung, distribution of deposited and suspended particles toward the right lung exceeded that of the left lung. The CFD simulations also predict that for both 3 and 6 μm particles, aerosol distribution between lung units subtending from airways in generation 5 did not match gas distribution between these units and that this effect was driven by inertial impaction.Conclusions: We showed combined imaging experiments and CFD simulations to systematically study aerosol deposition patterns in human airways down to generation 5, where particle deposition could be spatially linked to the airway geometry. As particles are negotiating an increasing number of airways in subsequent branching generations, CFD predicts marked dev
Biddiscombe M, Matthews J, Wright M, et al., 2015, CHARACTERISATION OF A HIGH VOLTAGE CORONA CHARGER TO SIMULATE THE AEROSOL CHARGE STATE FOUND NEAR HV POWER LINES
Matthews JC, Wright MD, Biddiscombe MF, et al., 2015, Re-creation of aerosol charge state found near HV power lines using a high voltage corona charger, Conference on Electrostatics, Publisher: IOP Publishing, ISSN: 1742-6588
Biddiscombe MF, Murdoch RD, Allen A, et al., 2014, Aerosol Particle Size Influences The Fate Of Inhaled Corticosteroids In Asthma, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 189, ISSN: 1073-449X
Biddiscombe M, Kalsi H, Meah S, et al., 2013, The fate of inhaled drug: Corticosteroid particle size effects in asthma, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
Wright MD, Matthews JC, Biddiscombe MF, et al., 2013, LUNG DEPOSITION OF CHARGED AEROSOL PARTICLES - CHARGE CHARACTERISATION USING ELPI AND HUMAN VOLUNTEER STUDY, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 26, Pages: A252-A252, ISSN: 1941-2711
Kalsi HS, Biddiscombe MF, Usmani OS, 2013, MONODISPERSE AEROSOL DEPOSITION IN COMPARTMENTS OF THE EXTRA-THORACIC AIRWAY: IN VIVO, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 26, Pages: A25-A25, ISSN: 1941-2711
Kalsi HS, Biddiscombe MF, Meah S, et al., 2013, THERAPEUTIC AEROSOL PARTICLE DEPOSITION IN COMPARTMENTS OF THE EXTRA-THORACIC AIRWAY: COMPARISON OF IN VIVO AND IN VITRO, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 26, Pages: A36-A37, ISSN: 1941-2711
Biddiscombe MF, Verbanck S, Kalsi H, et al., 2013, THE MULTIPLE BREATH WASHOUT TEST AS A TOOL FOR ASSESSING PERIPHERALLY TARGETED THERAPEUTIC DRUGS: ESTABLISHING A NORMAL RANGE IN HEALTHY VOLUNTEERS, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 26, Pages: A27-A28, ISSN: 1941-2711
Newman S, Bennett WD, Biddiscombe M, et al., 2012, Standardization of Techniques for Using Planar (2D) Imaging for Aerosol Deposition Assessment of Orally Inhaled Products, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 25, Pages: S10-S28, ISSN: 1941-2711
Biddiscombe MF, Usmani OS, 2012, The importance of imaging and physiology measurements in assessing the delivery of peripherally targeted aerosolized drugs., Ther Deliv, Vol: 3, Pages: 1329-1345, ISSN: 2041-5990
Considerable recent effort has been directed towards developing new aerosol formulations and delivery devices that can target drugs to the lung periphery. In order to determine the efficacy of targeted drug therapy, it is essential that the peripheral lung region be adequately assessed. Imaging of the airways structure and pathology has greatly advanced in the last decade and this rate of growth is accelerating as new technologies become available. Lung imaging continues to play an important role in the study of the peripheral airways and, when combined with state-of-the-art lung function measurements and computational modeling, can be a powerful tool for investigating the effects of inhaled medication. This article focuses on recent strategies in imaging and physiological measurements of the lungs that allow the assessment of inhaled medication delivered to the periphery and discusses how these methods may help to further optimize and refine future aerosol delivery technology.
Verbanck S, Thompson BR, Schuermans D, et al., 2012, Ventilation heterogeneity in the acinar and conductive zones of the normal ageing lung, THORAX, Vol: 67, Pages: 789-795, ISSN: 0040-6376
Thompson BR, Verbanck S, Schuermans D, et al., 2012, AGE DEPENDENCE OF SMALL AIRWAYS VENTILATION HETEROGENEITY, RESPIROLOGY, Vol: 17, Pages: 5-5, ISSN: 1323-7799
Biddiscombe MF, Meah SN, Underwood SR, et al., 2011, Comparing Lung Regions of Interest in Gamma Scintigraphy for Assessing Inhaled Therapeutic Aerosol Deposition, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, Vol: 24, Pages: 165-173, ISSN: 1941-2711
Kalsi H, Biddiscombe MF, Verbanck S, et al., 2011, MONODISPERSE AEROSOL DEPOSITIONIN UPPER AIRWAY MODELS:INSPIRATION VS. EXPIRATION, International Society for Aerosols in Medicine, Publisher: Mary Ann Liebert
Background: In vitro methods are practical and convenientfor determining patterns of upper airway aerosol deposition.They allow for control of relevant deposition variables includingbreathing pattern and particle size. In this study, the effects ofaerosol particle size, flow rate and flow direction were investigatedon upper airway deposition in vitro.Methods: Regions of interest (ROI’s) were defined (oral, pharynx,larynx, trachea) in 4 identical silicone upper airway models to a spinning-top aerosol generator at one end and a suction pumpat the other depending on flow direction (inspiration/expiration).Radiolabelled salbutamol solutions were delivered as monodisperse3 or 6 m aerosols at 30 or 60 L/min. Gamma-scintigraphywas used to determine deposition efficiency.Conclusions: While total deposition efficiency was similar betweeninspiration and expiration, deposition in the ROI’s showedvery different distribution patterns. These patterns were consistentand somewhat dependent on flow rate and particle size.(UAM’s). The UAM’s interiors weremucus coated then connected
Matthews JC, Wright MD, Biddiscombe MF, et al., 2011, HUMAN VOLUNTEER INHALATIONAND LUNG DEPOSITIONOF CHARGED AEROSOLS - CHARACTERISATIONOF CHARGE STATE USING AN ELPI, International Society for Aerosols in Medicine
Effects of particle electric charge state are important to theefficiency of drug delivery to the lung and possibly to exposureto pollutants charged by corona ions near high voltage powerlines. We plan to test whether 100 and 200nm particles withexcess charge have a higher probability of lung deposition thancharge-neutralised particles, when inhaled by healthy volunteers.The study requires characterisation of both the charge stateand size of inhaled particles.The extent of aerosol charging can be examined using anElectrical Low Pressure Impactor (ELPI), a cascade impactorwith an internal corona charger. The current on each impactorstage is measured and the size distribution obtained in conjunctionwith the charging probability. To test the proposedmethodology, the ELPI was used to measure ambient aircharged by a negative air ioniser. The ELPI internal charger wasswitched on and off at 30 s intervals to allow alternate, on-linemeasurement of both size and charge distributions.The modal average concentration and inter-quartile range of120 and 200nm particles, with the internal corona charger on,was 2000 194 and 1217 132 cm 3 respectively. The averageambient charge per particle (with internal charger off) was estimatedat 0.6 and 1.1 e, respectively. In conclusion, the ELPI canbe used effectively, through regular switching of the coronacharger, to estimate the average charge of aerosols.
Usmani OS, Biddiscombe MF, Meah S, et al., 2011, ASSESSING SMALL AND LARGE AIRWAYRESPONSES TO INHALED BRONCHODILATOR DRUGTARGETED TO REGIONAL LUNG COMPARTMENTSIN ASTHMATICS, International Society for Aerosols in Medicine, Publisher: Mary Ann Liebert
Purpose: We have shown changing aerosol particle size targetsinhaled bronchodilator drug to different lung regions inasthmatics, where larger (6 & 3 m) particles achieved greaterspirometric improvements. However, we reasoned spirometrycould not distinguish airway responses of the small (1.5 m)particles depositing in the distal lung regions. We used a morespecific test of small airway function, multibreath-N2-washout(MBN2W), to assess changes in ventilation heterogeneity (VH)from proximal (conducting, Scond) and distal (acinar, Sacin)lung compartments.Methods: MBN2W indices were assessed at baseline & 20minutes after inhalation of 30 g radiolabelled 6, 3 & 1.5 msalbutamol particles in 13 mild-moderate asthmatics.Results: Abnormalities in both Scond and Sacin were detectedat baseline. Larger salbutamol particles deposited in proximalairways, achieved more bronchodilation (FEV1) and producedgreater improvements in VH of proximal airways (Scond),compared to smaller particles (1.5 m). Interestingly, althoughsmaller particles did not achieve as much bronchodilationcompared to larger particles, they produced the greatest improvementin VH of the distal airways (Sacin).Conclusions: MBN2W indices can accurately elicit airwayresponses from different lung compartments. The observedchanges in MBN2W are compatible with regional lung targetingof inhaled bronchodilator drug, where a more peripheral airwayresponse was elicited by the smaller bronchodilator aerosols.
Biddiscombe MF, Underwood SR, Meah S, et al., 2011, DEFINING REGIONAL LUNG DEPOSITION IN 2-DGAMMA SCINTIGRAPHY, International Society for Aerosols in Medicine, Publisher: Mary Ann Liebert
Introduction: Two-dimensional gamma scintigraphy (2DGS)is used for quantifying drug delivery from therapeutic inhalerdevices to the lungs. Images are divided into central (C) andperipheral (P) regions. No standard method exists.Purpose: To compare 6 methods of partitioning lung images.Methods 1 and 2 include an intermediate region (I).Methods: We calculated three lung penetration indices: C/Pcounts ratio, P/C counts ratio, and Penetration Index (PI) formonodisperse aerosols (1.5 m, 3.0 m and 6.0 m MMAD).PI¼ratio of P/C counts for deposition aerosol normalised by P/C counts for a krypton-ventilation scan.Results: The lung areas of C (20 - 32%) and P (50 - 80%) regionsvaried greatly depending on the method. This was reflected in theC/P and P/C ratios. However, there was good agreement of PI.Particle size had a significant effect on the results.Conclusions: The most important difference between themethods was the size and shape of the P regions. PI is leastaffected by how the lung regions are drawn and should be theprimary endpoint to compare results from different scintigraphiclung deposition studies.C/P1.5 m: Mean 0.75 0.15, (SD¼19.6%)3.0 m: Mean 1.27 0.32, (SD¼24.8 %)6.0 m: Mean 1.48 0.39, (SD¼26.3%)P/C1.5 m: Mean 1.41 0.33, (SD¼23.4%)3.0 m: Mean 0.86 0.31, (SD¼35.4 %)6.0 m: Mean 0.77 0.28, (SD¼36.4%)PI1.5 m: Mean 0.77 0.02, (SD¼2.4%)3.0 m: Mean 0.47 0.06, (SD¼13.2%)6.0 m: Mean 0.42 0.06, (SD¼14.8%)
Verbanck S, Kalsi HS, Biddiscombe MF, et al., 2011, Inspiratory and expiratory aerosol deposition in the upper airway, INHALATION TOXICOLOGY, Vol: 23, Pages: 104-111, ISSN: 0895-8378
Verbanck S, Biddiscombe MF, Kalsi HS, et al., 2011, Inspiratory And Expiratory Aerosol Deposition In The Upper Airway, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Matthews JC, Wright MD, Biddiscombe MF, et al., 2011, Aerosol charge state characterisation using an ELPI, PROCEEDINGS OF THE 13TH INTERNATIONAL CONFERENCE ON ELECTROSTATICS: ELECTROSTATICS 2011, Vol: 301, ISSN: 1742-6588
de Matas M, Shao Q, Biddiscombe MF, et al., 2010, Predicting the clinical effect of a short acting bronchodilator in individual patients using artificial neural networks, EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, Vol: 41, Pages: 707-715, ISSN: 0928-0987
Biddiscombe MF, Verbanck S, Meah S, et al., 2009, REPRODUCIBILITY OF THE MULTIPLE BREATH NITROGEN WASHOUT TEST IN HEALTHY VOLUNTEERS AND SUBJECTS WITH MILD TO MODERATE ASTHMA, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A128-A128, ISSN: 0040-6376
Biddiscombe MF, Meah S, Barnes PJ, et al., 2009, GAMMA SCINTIGRAPHY: REGIONS OF INTEREST IN THE LUNGS. ARE WE BEING CONSISTENT IN WHAT WE ARE MEASURING?, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A153-A154, ISSN: 0040-6376
de Matas M, Shao Q, Biddiscombe M, et al., 2009, MODELLING THE IMPACT OF INHALED DRUG PARTICLE SIZE OF SALBUTAMOL ON BRONCHODILATOR RESPONSE USING ARTIFICIAL INTELLIGENCE, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A131-A131, ISSN: 0040-6376
Biddiscombe MF, Meah S, Sadler R, et al., 2009, IN VITRO VALIDATION OF RADIOLABELLED INHALED CORTICOSTEROID FOR IN VIVO LUNG DELIVERY USING GAMMA SCINTIGRAPHY, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A131-A132, ISSN: 0040-6376
Biddiscombe MF, Barnes PJ, Usmani OS, 2006, Generating monodisperse pharmacological aerosols using the spinning-top aerosol generator, JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG, Vol: 19, Pages: 245-253, ISSN: 0894-2684
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