help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on September 28, 2005, doi:10.1164/rccm.200410-1414OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 12, December 2005, 1497-1504

A more recent version of this article appeared on December 15, 2005
This Article
Right arrow Full Text (PDF)
Right arrow Editorial
Right arrow All Versions of this Article:
200410-1414OCv1
172/12/1497    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Usmani, O. S
Right arrow Articles by Barnes, P. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Usmani, O. S
Right arrow Articles by Barnes, P. J

Submitted on October 26, 2004
Accepted on September 23, 2005

Regional Lung Deposition and Bronchodilator Response as a Function of {beta}2-agonist Particle Size

Omar S Usmani1*, Martyn F Biddiscombe2, and Peter J Barnes1

1 Department of Thoracic Medicine, Imperial College London, National Heart and Lung Institute, London, United Kingdom, 2 Department of Nuclear Medicine, Royal Brompton Hospital, London, United Kingdom

* To whom correspondence should be addressed. E-mail: o.usmani{at}imperial.ac.uk.

Rationale: Aerosol particle size influences the extent, distribution and site of inhaled drug deposition within the airways. Objectives: We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery. Methods: In a randomized, double-blind, placebo-controlled study, 12 asthmatic subjects (FEV1 76.8±11.4% predicted) inhaled technetium-99m-labeled monodisperse albuterol aerosols (30µg-dose)of 1.5µm, 3µm, and 6µm mass median aerodynamic diameter, at slow (30-60 l/min) and fast (>60 l/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigrapy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15µg-dose) and 200µg MDI albuterol. Results: Smaller particles achieved greater total lung deposition: 1.5µm(56%), 3µm(50%), 6µm(46%), further distal airways penetration (0.79, 0.60, 0.36, respective penetration index), and more peripheral lung deposition (25%, 17%, 10%, respectively). However, larger particles (30µg-dose) were more efficacious, and achieved greater bronchodilation than 200µg MDI albuterol; {Delta}FEV1(ml); 6µm(551), 3µm(457), 1.5µm(347), MDI(494). Small particles were exhaled more 1.5µm(22%), 3µm(8%), 6µm(2%), whereas greater oropharyngeal deposition occurred with large particles (15%, 31%, 43%, respectively). Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles with less bronchodilation. A shift in aerosol distribution to the proximal airways was observed for all particles. Conclusions: Regional targeting of inhaled {beta}2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.
Key words: Aerosol, Particle Size, Radionuclide Imaging, Asthma, Beta-Adrenergic Agonists




This article has been cited by other articles:


Home page
 Proc Am Thorac SocHome page
M. B. Dolovich
18F-Fluorodeoxyglucose Positron Emission Tomographic Imaging of Pulmonary Functions, Pathology, and Drug Delivery
Proceedings of the ATS, August 15, 2009; 6(5): 477 - 485.
[Abstract] [Full Text] [PDF]

Home page
 ERRHome page
P-R. Burgel, J. de Blic, P. Chanez, C. Delacourt, P. Devillier, A. Didier, J-C. Dubus, I. Frachon, G. Garcia, M. Humbert, et al.
Update on the roles of distal airways in asthma
Eur. Respir. Rev., June 1, 2009; 18(112): 80 - 95.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
D. W. Porter, A. F. Hubbs, P. A. Baron, L. L. Millecchia, M. G. Wolfarth, L. A. Battelli, D. E. Schwegler-Berry, C. M. Beighley, M. E. Andrew, and V. Castranova
Pulmonary Toxicity of Expancel(R) Microspheres in the Rat
Toxicol Pathol, August 1, 2007; 35(5): 702 - 714.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
R. A.M. Al-Showair, S. B. Pearson, and H. Chrystyn
The Potential of a 2Tone Trainer To Help Patients Use Their Metered-Dose Inhalers
Chest, June 1, 2007; 131(6): 1776 - 1782.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
G. Horvath, N. Schmid, M. A. Fragoso, A. Schmid, G. E. Conner, M. Salathe, and A. Wanner
Epithelial Organic Cation Transporters Ensure pH-Dependent Drug Absorption in the Airway
Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 53 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. E. Wenzel and R. Covar
Update in asthma 2005.
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 698 - 706.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2005 American Thoracic Society 		  New Orleans Int'l Conf