The University of Southampton
University of Southampton Institutional Repository

Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation

Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation
Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation
Background: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out.
Objectives: We compared changes in AHR to inhaled methacholine and adenosine 5?-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, placebo-controlled, crossover study of patients with mild-to-moderate asthma. Subsequently, we undertook a separate study to examine the time course of the changes in AHR in more detail and the changes in sputum cell counts in relation to budesonide treatment.
Methods: In the phase 1 of the study, patients undertook bronchial provocation studies with increasing doubling concentrations of methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled agonists were expressed as the provocative concentration causing a 20% decline in FEV1 (PC20). In phase 2 of the study, patients attended the laboratory on 12 separate occasions to investigate changes in PC20 methacholine, PC20 AMP, and sputum cell counts before, during, and after withdrawal of therapy with inhaled budesonide 0.8 mg/daily for 6 weeks.
Results: Budesonide treatment for 3 weeks significantly attenuated the constrictor response by 0.8 ± 0.3 doubling doses for methacholine and by 2.6 ± 0.5 doubling doses for AMP. These changes were significantly different from each other (P = .003). Significant variation in PC20 methacholine (P < .05) value, PC20 AMP (P < .001) value, percentage of sputum eosinophils (P < .001), and percentage of sputum epithelial cells (P < .001) were observed throughout the longitudinal assessment of changes in airway response to budesonide. Compared with the other surrogate markers, PC20 AMP appears to be useful in promptly detecting early inflammatory changes of the asthmatic airways; a significant change of 1.6 ± 0.3, 2.2 ± 0.3, and 2.8 ± 0.3 doubling doses of PC20 AMP was observed at 1, 4, and 6 weeks, respectively, in the course of budesonide treatment.
Conclusions: The present findings underline the exquisite selectivity of diverse surrogate markers of airway inflammation in response to inhaled budesonide. When compared with that to the other markers, AHR to inhaled AMP is an early and sensitive indicator of the beneficial anti-inflammatory effects of topical GCSs.
0091-6749
855-861
Prosperini, Gaetano
15d2c26f-4a78-4a11-bdaa-dc3ade9263bd
Rajakulasingam, Kajakulasingam
a327166d-fce4-4bbd-ab8e-704bf8bf0a76
Cacciola, Rossella R.
0218d6dd-bf55-456a-8bd6-5063b0c380e8
Spicuzza, Lucia
6da32b9b-c81a-4813-8062-d301cc1722c3
Rorke, Steuart
0b362590-4c4d-47f6-b09b-988ae79f6994
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Di Maria, Giuseppe U.
52e46dce-45e0-4bf3-9261-0ad286bbc44b
Polosa, Riccardo
8eaf4eb4-d2fc-4e22-b6c7-e9a2e28d95ec
Prosperini, Gaetano
15d2c26f-4a78-4a11-bdaa-dc3ade9263bd
Rajakulasingam, Kajakulasingam
a327166d-fce4-4bbd-ab8e-704bf8bf0a76
Cacciola, Rossella R.
0218d6dd-bf55-456a-8bd6-5063b0c380e8
Spicuzza, Lucia
6da32b9b-c81a-4813-8062-d301cc1722c3
Rorke, Steuart
0b362590-4c4d-47f6-b09b-988ae79f6994
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Di Maria, Giuseppe U.
52e46dce-45e0-4bf3-9261-0ad286bbc44b
Polosa, Riccardo
8eaf4eb4-d2fc-4e22-b6c7-e9a2e28d95ec

Prosperini, Gaetano, Rajakulasingam, Kajakulasingam, Cacciola, Rossella R., Spicuzza, Lucia, Rorke, Steuart, Holgate, Stephen T., Di Maria, Giuseppe U. and Polosa, Riccardo (2002) Changes in sputum counts and airway hyperresponsiveness after budesonide: monitoring anti-inflammatory response on the basis of surrogate markers of airway inflammation. Journal of Allergy and Clinical Immunology, 110 (6), 855-861. (doi:10.1067/mai.2002.130050).

Record type: Article

Abstract

Background: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out.
Objectives: We compared changes in AHR to inhaled methacholine and adenosine 5?-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, placebo-controlled, crossover study of patients with mild-to-moderate asthma. Subsequently, we undertook a separate study to examine the time course of the changes in AHR in more detail and the changes in sputum cell counts in relation to budesonide treatment.
Methods: In the phase 1 of the study, patients undertook bronchial provocation studies with increasing doubling concentrations of methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled agonists were expressed as the provocative concentration causing a 20% decline in FEV1 (PC20). In phase 2 of the study, patients attended the laboratory on 12 separate occasions to investigate changes in PC20 methacholine, PC20 AMP, and sputum cell counts before, during, and after withdrawal of therapy with inhaled budesonide 0.8 mg/daily for 6 weeks.
Results: Budesonide treatment for 3 weeks significantly attenuated the constrictor response by 0.8 ± 0.3 doubling doses for methacholine and by 2.6 ± 0.5 doubling doses for AMP. These changes were significantly different from each other (P = .003). Significant variation in PC20 methacholine (P < .05) value, PC20 AMP (P < .001) value, percentage of sputum eosinophils (P < .001), and percentage of sputum epithelial cells (P < .001) were observed throughout the longitudinal assessment of changes in airway response to budesonide. Compared with the other surrogate markers, PC20 AMP appears to be useful in promptly detecting early inflammatory changes of the asthmatic airways; a significant change of 1.6 ± 0.3, 2.2 ± 0.3, and 2.8 ± 0.3 doubling doses of PC20 AMP was observed at 1, 4, and 6 weeks, respectively, in the course of budesonide treatment.
Conclusions: The present findings underline the exquisite selectivity of diverse surrogate markers of airway inflammation in response to inhaled budesonide. When compared with that to the other markers, AHR to inhaled AMP is an early and sensitive indicator of the beneficial anti-inflammatory effects of topical GCSs.

This record has no associated files available for download.

More information

Published date: 2002

Identifiers

Local EPrints ID: 27344
URI: http://eprints.soton.ac.uk/id/eprint/27344
ISSN: 0091-6749
PURE UUID: b31d5330-202b-4f19-9c4f-fd78031fc7f4

Catalogue record

Date deposited: 27 Apr 2006
Last modified: 15 Mar 2024 07:17

Export record

Altmetrics

Contributors

Author: Gaetano Prosperini
Author: Kajakulasingam Rajakulasingam
Author: Rossella R. Cacciola
Author: Lucia Spicuzza
Author: Steuart Rorke
Author: Giuseppe U. Di Maria
Author: Riccardo Polosa

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×