Lung Computational Models and the Role of the Small Airways in Asthma

Foy, Brody H.; Soares, Marcia; Bordas, Rafel; Richardson, Matthew; Bell, Alex; Singapuri, Amisha; Hargadon, Beverley; Brightling, Christopher; Burrowes, Kelly; Kay, David; Owers-Bradley, John; Siddiqui, Salman

Abstract

RATIONALE: Asthma is characterised by disease within the small airways. Several studies have suggested that forced oscillation technique derived resistance at 5Hz minus 20Hz (R5-R20) is measure of small airways disease, however there has been limited validation of this measurement to date. METHODS: Patient based complete conducting airway models were generated from CT scans to simulate the impact of different degrees of airway narrowing at different levels of the airway tree on forced oscillation R5-R20 (n=31). The computational models were coupled with regression models in an asthmatic cohort (n=177), to simulate the impact of small airway narrowing on asthma control and quality of life. The computational models were used to predict the impact on small airway narrowing of type-2 targeting biologics using pooled data from two similarly design randomised placebo control biologic trials (n=137). RESULTS: Simulations demonstrated that narrowing of the small airways had a greater impact on R5-R20 than narrowing of the larger airways and was associated (above a threshold of approximately 40% narrowing) with marked deterioration in both asthma control and asthma quality of life, above the minimal clinical important difference. The observed treatment effect on R5-R20 in the pooled trials equated to a predicted small airway narrowing reversal of approximately 40%. CONCLUSIONS: We have demonstrated using computational modelling that forced oscillation R5-R20 is a direct measure of anatomical narrowing in the small airways, that small airway narrowing has a marked impact on both asthma control and quality of life and may be modified by biologics.

Citation

Foy, B. H., Soares, M., Bordas, R., Richardson, M., Bell, A., Singapuri, A., Hargadon, B., Brightling, C., Burrowes, K., Kay, D., Owers-Bradley, J., & Siddiqui, S. (2019). Lung Computational Models and the Role of the Small Airways in Asthma. American Journal of Respiratory and Critical Care Medicine, 200(8), 982-991. https://doi.org/10.1164/rccm.201812-2322oc

• Journal Article Type: Article
• Acceptance Date: May 14, 2019
• Online Publication Date: May 18, 2019
• Publication Date: 2019-05
• Deposit Date: Jun 3, 2019
• Publicly Available Date: May 19, 2020
• Journal: American Journal of Respiratory and Critical Care Medicine
• Print ISSN: 1073-449X
• Electronic ISSN: 1535-4970
• Publisher: American Thoracic Society
• Peer Reviewed: Peer Reviewed
• Volume: 200
• Issue: 8
• Pages: 982-991
• DOI: https://doi.org/10.1164/rccm.201812-2322oc
• Keywords: Asthma; Forced oscillation technique, Small airways, Imaging, Computational modelling, Integrative modelling
• Public URL: https://nottingham-repository.worktribe.com/output/2131098
• Publisher URL: https://www.atsjournals.org/doi/10.1164/rccm.201812-2322OC
• Contract Date: Jun 4, 2019