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The Topical Study Of Inhaled Drug (salbutamol) Delivery In Idiopathic Pulmonary Fibrosis

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Title: The Topical Study Of Inhaled Drug (salbutamol) Delivery In Idiopathic Pulmonary Fibrosis
Authors: Maher, TM
Biddiscombe, M
Fahy, WA
Lukey, P
Marshall, RP
Meah, S
Oballa, E
Simpson, JK
Yang, S
Usmani, O
Item Type: Journal Article
Abstract: Background Our aim was to investigate total and regional lung delivery of salbutamol in subjects with idiopathic pulmonary fibrosis (IPF). Methods The 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). Results Small 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. Conclusion Our 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.
Issue Date: 6-Feb-2018
Date of Acceptance: 31-Jan-2018
URI: http://hdl.handle.net/10044/1/57340
DOI: https://dx.doi.org/10.1186/s12931-018-0732-0
ISSN: 1465-9921
Publisher: BioMed Central
Journal / Book Title: Respiratory Research
Volume: 19
Issue: 1
Copyright Statement: © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Royal Brompton & Harefield NHS Foundation Trust
Funder's Grant Number: N/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
Gamma scintigraphy
Idiopathic pulmonary fibrosis (IPF)
Inhaled drug delivery
11 Medical And Health Sciences
Publication Status: Published
Conference Place: Washington, DC
Article Number: 25
Appears in Collections:National Heart and Lung Institute