Characterising the role of small airways in severe asthma using low frequency forced oscillations: A combined computational and clinical approach

Foy, Brody H.; Natarajan, Sushiladevi; Munawar, Arham; Soares, Marcia; Thorpe, James; Owers-Bradley, John; Siddiqui, Salman

Abstract

Background:
Within asthma, the small airways (? 2mm in diameter) play an important role in pathophysiology. Using a combined clinical-computational approach, we sought to more precisely evaluate the contribution of the small airways to deep-breath induced airway dilation (in the absence of bronchial challenge), which may be impaired in severe asthma.

Methods:
A patient-based computational model of the FOT was used to examine the sensitivity and specificity of FOT signals to small airways constriction at frequencies of 2 & 8 Hz. A clinical study of moderate to severe asthmatics (n=24), and healthy volunteers (n=10) was performed to evaluate correlations between baseline and post deep inspiration (following bronchodilator withhold and in the absence of prior bronchial challenge) forced oscillation technique (FOT) responses (at 2Hz and 8Hz) and asthma treatment intensity, spirometry, airway hyper-responsiveness and airway inflammation.

Results:
Computational modelling demonstrated that baseline resistance measures at 2Hz are both sensitive and specific to anatomical narrowing in the small airways. Furthermore, small airways resistance was significantly increased in asthmatics compared to health. Despite these differences, there were no noticeable differences between asthmatics and healthy volunteers in resistive measures following deep inspiration (DI) and DI responses of small airways were amplified in the presence of spirometry defined airflow limitation.

Conclusions:
These results suggest that the small airways demonstrate increased resistance in moderate-to-severe asthma but dilate normally in response to deep inspirations in the absence of bronchial challenge. This suggests that effective targeting of the small airways is required to achieve functional improvements in moderate-severe asthmatic patients.

Citation

Foy, B. H., Natarajan, S., Munawar, A., Soares, M., Thorpe, J., Owers-Bradley, J., & Siddiqui, S. (2020). Characterising the role of small airways in severe asthma using low frequency forced oscillations: A combined computational and clinical approach. Respiratory Medicine, 170, Article 106022. https://doi.org/10.1016/j.rmed.2020.106022

• Journal Article Type: Article
• Acceptance Date: May 11, 2020
• Publication Date: May 18, 2020
• Deposit Date: Jul 31, 2020
• Publicly Available Date: May 19, 2021
• Journal: Respiratory Medicine
• Print ISSN: 0954-6111
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 170
• Article Number: 106022
• DOI: https://doi.org/10.1016/j.rmed.2020.106022
• Keywords: asthma, forced oscillation technique, deep inspiration, computational, small airways.
• Public URL: https://nottingham-repository.worktribe.com/output/4798344
• Publisher URL: https://www.resmedjournal.com/article/S0954-6111(20)30162-1/fulltext
• Additional Information: This article is maintained by: Elsevier; Article Title: Characterising the role of small airways in severe asthma using low frequency forced oscillations: A combined computational and clinical approach; Journal Title: Respiratory Medicine; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.rmed.2020.106022; Content Type: article; Copyright: © 2020 Elsevier Ltd. All rights reserved.