The contribution of ventilation imaging to the understanding of airway hyperresponsiveness in asthma

Abstract

Background Asthma is characterised by episodic airway closure and airway narrowing during bronchoconstriction. The causes and mechanisms of airway closure and narrowing in asthma are still poorly understood and investigation of these areas will contribute to improved treatment strategies and patient outcomes. The extent of lung affected by airway closure and narrowing during bronchoconstriction can potentially be measured by 3-dimensional ventilation imaging. Ventilation Single Photon Emission Computed Tomography (VSPECT) using Technegas as the imaging agent, combined with Computed Tomography (CT), is routinely used for detection of pulmonary embolism as part of a ventilation/perfusion scan. This technique has been adapted for use in research to measure ventilation distribution The small airways are an important compartment of the bronchial tree in asthma. Their function can be measured as ventilation heterogeneity, using the Multiple Breath Nitrogen Washout test (MBNW). MBNW parameters have important clinical correlates in asthma, such as with airway hyperresponsiveness, asthma control and exacerbation risk. «br /» As it is known that the small airways are important functionally in asthma, then small airway function may be an important determinant of the patterns of airway narrowing and of airway closure in asthma. Furthermore, abnormalities in small airway function may determine the extent of airway narrowing and closure that is visualised topographically. The aim of this thesis was to investigate the role of the small airways in determining the severity of airway narrowing and closure in asthma. Small airways function was measured using the Multiple Breath Nitrogen Washout test (MBNW) and ventilation imaging was performed using Ventilation Single Photon Emission Computed Tomography (VSPECT). The aims of the studies described in this thesis were to: 1. investigate the recovery of small airway function as measured by MBNW, from methacholine challenge in asthmatic subjects; 2. determine the predictors of airway narrowing and of airway closure on VSPECT/CT, including ventilation heterogeneity and airway hyperresponsiveness, in asthmatic subjects; 3. determine whether closure occurs following high dose methacholine challenge (MCh) in healthy, non-asthmatic subjects measured by VSPECT/CT and to examine relationships with changes in lung function Results We found that there was a recovery in acinar airway function following methacholine induced bronchoconstriction, over the course of a MBNW. Therefore, the results of MBNW post-methacholine reflect the mean of small airways function during a period where small airways function is improving. Asthmatic airway closure on VSPECT/CT was predicted independently by both airway hyperresponsiveness and by conductive small airway function measured by MNBW. This suggests that small airway function is a determinant of excessive bronchoconstriction, which was also independent of the changes in FEV1. Asthmatic airway narrowing, measured separately on VSPECT/CT, was predicted by acinar airway function measured by MBNW. This suggests that the very peripheral airways influence that pattern of narrowing during bronchoconstrictor response in asthma. The VSPECT/CT studies showed that healthy non-asthmatics demonstrate airway closure during methacholine induced bronchoconstriction. The pattern was subjectively more patchy in asthmatic compared with healthy subjects. In non-asthmatic subjects, the extent of closure correlated with changes in FEV1. Summary and conclusions Peripheral airway function, of both acinar and conductive airways, has a strong influence on the pattern of airway narrowing and closure as seen in VSPECT/CT scans in asthma. Combined with the known clinical correlations of acinar and conductive airways dysfunction in asthma, these findings further support the importance of the small airways in the physiology and clinical expression of asthma. Therefore it is reasonable to suggest that improving small airway function will not only lead to changes in the bronchoconstrictor response as measured by 3-D imaging, but will also show corresponding improvements in asthma control. However, this needs to be determined by future studies.