Alex J Bell1, Brody H Foy2, Matthew Richardson1, Amisha Singapuri1, Evgeny Mirkes3, Maarten van den Berge4, David Kay2, Chris Brightling1, Alexander N Gorban3, Craig J Galbán5, Salman Siddiqui6. 1. NIHR Respiratory Biomedical Research Centre (BRC), Department of Respiratory Sciences, University of Leicester, Leicester, United Kingdom. 2. Computational Biology, Department of Computer Science, University of Oxford, Oxford, United Kingdom. 3. Department of Mathematics, University of Leicester, Leicester, United Kingdom. 4. Department of Pulmonology, University Medical Centre Groningen, Groningen, the Netherlands. 5. Department of Radiology, University of Michigan, Ann Arbor, Mich. 6. NIHR Respiratory Biomedical Research Centre (BRC), Department of Respiratory Sciences, University of Leicester, Leicester, United Kingdom. Electronic address: ss338@leicester.ac.uk.
Abstract
BACKGROUND: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient-related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood. OBJECTIVES: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients. METHODS: We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n = 41) and healthy (n = 11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (ΔHU); gradients of ΔHU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified. RESULTS: The ΔHU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5 Hz minus resistance at 20 Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior ΔHU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. A computational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small-airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency. CONCLUSIONS: Lower lobe-predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.
BACKGROUND: Asthma is a disease characterized by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived by using impulse oscillometry (IOS) or multiple-breath washout (MBW) are associated with key asthmatic patient-related outcome measures and airways hyperresponsiveness. However, the topographical mechanisms of VH in the lung remain poorly understood. OBJECTIVES: We hypothesized that specific regionalization of topographical small-airway disease would best account for IOS- and MBW-measured indices in patients. METHODS: We evaluated the results of paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n = 41) and healthy (n = 11) volunteers to understand the determinants of clinical VH indices commonly reported by using IOS and MBW. Parametric response mapping (PRM) was used to calculate the functional small-airways disease marker PRMfSAD and Hounsfield unit (HU)-based density changes from total lung capacity to functional residual capacity (ΔHU); gradients of ΔHU in gravitationally perpendicular (parallel) inferior-superior (anterior-posterior) axes were quantified. RESULTS: The ΔHU gradient in the inferior-superior axis provided the highest level of discrimination of both acinar VH (measured by using phase 3 slope analysis of multiple-breath washout data) and resistance at 5 Hz minus resistance at 20 Hz measured by using impulse oscillometry (R5-R20) values. Patients with a high inferior-superior ΔHU gradient demonstrated evidence of reduced specific ventilation in the lower lobes of the lungs and high levels of PRMfSAD. A computational small-airway tree model confirmed that constriction of gravitationally dependent, lower-zone, small-airway branches would promote the largest increases in R5-R20 values. Ventilation gradients correlated with asthma control and quality of life but not with exacerbation frequency. CONCLUSIONS: Lower lobe-predominant small-airways disease is a major driver of clinically measured VH in adults with asthma.
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Authors: James G Krings; Charles W Goss; Daphne Lew; Maanasi Samant; Mary Clare McGregor; Jonathan Boomer; Leonard B Bacharier; Ajay Sheshadri; Chase Hall; Joshua Brownell; Ken B Schechtman; Samuel Peterson; Stephen McEleney; David T Mauger; John V Fahy; Sean B Fain; Loren C Denlinger; Elliot Israel; George Washko; Eric Hoffman; Sally E Wenzel; Mario Castro Journal: J Allergy Clin Immunol Date: 2021-02-09 Impact factor: 14.290
Authors: Orestes A Carpaij; Susan Muiser; Alex J Bell; Huib A M Kerstjens; Craig J Galban; Aleksa B Fortuna; Salman Siddiqui; Anna-Carin Olin; Martijn C Nawijn; Maarten van den Berge Journal: ERJ Open Res Date: 2019-10-21