Suchergebnisse

The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above. ; BACKGROUND: Asthma is a disease characterised by ventilation heterogeneity (VH). A number of studies have demonstrated that VH markers derived using impulse oscillometry (IOS) or multiple breath washout (MBW) are associated with key asthma patient related outcome measures and airways hyper responsiveness. However the topographical mechanisms of VH in the lung remain poorly understood. OBJECTIVES: We hypothesised that specific regionalisation of topographical small airway disease would best account for IOS and MBW measured indices in patients. METHODS: We evaluated paired expiratory/inspiratory computed tomography in a cohort of asthmatic (n=41) and healthy volunteers (n=11) to understand the determinants of clinical VH indices commonly reported using IOS and MBW. Parametric response mapping (PRM) was utilised to calculate functional small airways disease marker PRMfSAD and Hounsfield unit (HU) based density change from total lung capacity to functional residual capacity (ΔHU); gradients of ΔHU, in gravitationally perpendicular (parallel), inferior-superior (anterior-posterior) axes, were quantified. RESULTS: ΔHU gradient in the inferior-superior axis provided the highest level of discrimination of both Sacin and R5-20. 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 dependant lower zone small airway branches would promote the largest increases in R5-R20. 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 adult asthma. ; Supported by the Sir Jules Thorn trust, "Systems medicine: novel mathematical approaches to personalized care in asthma patients," through a clinical senior lecturer award (Professor Siddiqui). Additional funding was received for the original computed tomographic scan and physiologic analyses from Roche Pharmaceuticals (C.B. and S.S.) and the European Union Airways Disease Predicting Outcomes in Patient Specific Computational Models (AirPROM-FP7) consortium. This article was also supported by the National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Centre (BRC). ; Peer-reviewed ; Post-print