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Targeting the small airways with dry powder adenosine: a challenging concept

Background: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment. Objective: We aimed to identify these patients by selectively chal...

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Autores principales: van der Wiel, Erica, Lexmond, Anne J., van den Berge, Maarten, Postma, Dirkje S., Hagedoorn, Paul, Frijlink, Henderik W., Farenhorst, Martijn P., de Boer, Anne H., ten Hacken, Nick H. T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642194/
https://www.ncbi.nlm.nih.gov/pubmed/29057065
http://dx.doi.org/10.1080/20018525.2017.1369328
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author van der Wiel, Erica
Lexmond, Anne J.
van den Berge, Maarten
Postma, Dirkje S.
Hagedoorn, Paul
Frijlink, Henderik W.
Farenhorst, Martijn P.
de Boer, Anne H.
ten Hacken, Nick H. T.
author_facet van der Wiel, Erica
Lexmond, Anne J.
van den Berge, Maarten
Postma, Dirkje S.
Hagedoorn, Paul
Frijlink, Henderik W.
Farenhorst, Martijn P.
de Boer, Anne H.
ten Hacken, Nick H. T.
author_sort van der Wiel, Erica
collection PubMed
description Background: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment. Objective: We aimed to identify these patients by selectively challenging the small and large airways. We hypothesized that the airways could be challenged selectively using small- and large-particle adenosine, both inhaled at a high and a low flow rate. Design: In this cross-over study 11 asthma subjects performed four dry powder adenosine tests, with either small (MMAD 2.7 µm) or large (MMAD 6.0 µm) particles, inhaled once with a low flow rate (30 l min(–1)) and once with a high flow rate (60 l min(–1)). Spirometry and impulse oscillometry were performed after every bronchoprovocation step. We assumed that FEV(1) reflects the large airways, and FEF(25–75%), R5-R20 and X5 reflect the small airways. Results: The four adenosine tests were not significantly different with respect to the threshold values of FEV(1) (p = 0.12), FEF(25–75%) (p = 0.37), R5-R20 (p = 0.60) or X5 (p = 0.46). Both small- and large-particle adenosine induced a response in the small airways in the majority of the tests. Conclusions: In contrast to our hypothesis, all four adenosine tests provoked a response in the small airways and we could not identify different large- or small-airway responders. Interestingly, even the test with large particles and a high flow rate induced a small-airway response, suggesting that selective challenging of the small airways is not necessary. Future studies should investigate the relation between particle deposition and the site of an airway response.
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spelling pubmed-56421942017-10-20 Targeting the small airways with dry powder adenosine: a challenging concept van der Wiel, Erica Lexmond, Anne J. van den Berge, Maarten Postma, Dirkje S. Hagedoorn, Paul Frijlink, Henderik W. Farenhorst, Martijn P. de Boer, Anne H. ten Hacken, Nick H. T. Eur Clin Respir J Original Article Background: Small-particle inhaled corticosteroids (ICS) provide a higher small airway deposition than large-particle ICS. However, we are still not able to identify asthma patients who will profit most from small-particle treatment. Objective: We aimed to identify these patients by selectively challenging the small and large airways. We hypothesized that the airways could be challenged selectively using small- and large-particle adenosine, both inhaled at a high and a low flow rate. Design: In this cross-over study 11 asthma subjects performed four dry powder adenosine tests, with either small (MMAD 2.7 µm) or large (MMAD 6.0 µm) particles, inhaled once with a low flow rate (30 l min(–1)) and once with a high flow rate (60 l min(–1)). Spirometry and impulse oscillometry were performed after every bronchoprovocation step. We assumed that FEV(1) reflects the large airways, and FEF(25–75%), R5-R20 and X5 reflect the small airways. Results: The four adenosine tests were not significantly different with respect to the threshold values of FEV(1) (p = 0.12), FEF(25–75%) (p = 0.37), R5-R20 (p = 0.60) or X5 (p = 0.46). Both small- and large-particle adenosine induced a response in the small airways in the majority of the tests. Conclusions: In contrast to our hypothesis, all four adenosine tests provoked a response in the small airways and we could not identify different large- or small-airway responders. Interestingly, even the test with large particles and a high flow rate induced a small-airway response, suggesting that selective challenging of the small airways is not necessary. Future studies should investigate the relation between particle deposition and the site of an airway response. Taylor & Francis 2017-09-06 /pmc/articles/PMC5642194/ /pubmed/29057065 http://dx.doi.org/10.1080/20018525.2017.1369328 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
van der Wiel, Erica
Lexmond, Anne J.
van den Berge, Maarten
Postma, Dirkje S.
Hagedoorn, Paul
Frijlink, Henderik W.
Farenhorst, Martijn P.
de Boer, Anne H.
ten Hacken, Nick H. T.
Targeting the small airways with dry powder adenosine: a challenging concept
title Targeting the small airways with dry powder adenosine: a challenging concept
title_full Targeting the small airways with dry powder adenosine: a challenging concept
title_fullStr Targeting the small airways with dry powder adenosine: a challenging concept
title_full_unstemmed Targeting the small airways with dry powder adenosine: a challenging concept
title_short Targeting the small airways with dry powder adenosine: a challenging concept
title_sort targeting the small airways with dry powder adenosine: a challenging concept
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642194/
https://www.ncbi.nlm.nih.gov/pubmed/29057065
http://dx.doi.org/10.1080/20018525.2017.1369328
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