Asthmatic airway narrowing is heterogeneous and contributes to airway hyperresponsiveness. The present study compared heterogeneity of narrowing during methacholine challenge in asthmatics and normal subjects using high-resolution computed tomography (HRCT).The current authors defined heterogeneity as variability in narrowing greater than the repeatability of measurement. Airways of v2 mm diameter were compared with larger airways from baseline and postmethacholine HRCT of the right lower lung in 13 normals (seven had repeat baseline scans) and seven asthmatics. The coefficient of repeatability was calculated from repeat scans (RepAi) and was compared with heterogeneity of narrowing measured by the variability in narrowing from pre versus postmethacholine scans (VarDAi).Forced expiratory volume in one second decreased 27¡6% and 24¡8% in normals and asthmatics, respectively. Airways w2 mm narrowed more heterogeneously in asthmatics (VarDAi=¡0.85 mm) compared with normals (VarDAi=¡0.67 mm), with both being greater than the measure of repeatability (RepAi=¡0.16 mm). Small airway narrowing was not heterogeneous in asthmatics (VarDAi=¡0.59 mm) or normals (VarD Ai= ¡0.53 mm) compared with repeatability (RepAi=0.51 mm).It is possible to study heterogeneity of airway narrowing in small and large airways using high resolution computed tomography. Airway narrowing is heterogeneous in the large airways of asthmatics and normals, being greater in asthmatics.

Volume averaging results in both over-and underestimation of airway dimensions when they are measured by high-resolution computed tomography (HRCT). The current authors calibrated computerised measurements of airway dimensions from HRCT against a novel threedimensional micro-computed tomography (CT) standard, which has a 50-fold greater resolution, as well as against traditional morphometry.Inflation-fixed porcine lung cubes were scanned by HRCT and micro-CT. A total of 59 lumen area (Ai), 30 wall area (Aaw) and 11 lumen volume (Vi) measurements were made. Ai was measured from the cut surface of 11 airways by morphometry. Airways in scanned images were matched using branching points. After calibration, the errors of Ai, Aaw and Vi HRCT measurements were determined.The current authors found a systematic, size-dependent underestimation of Ai and overestimation of Aaw from HRCT measurements. This was used to calibrate an HRCT measurement algorithm. The 95% limits of agreement of subsequent measurements were ¡3.2 mm 2 for Ai, ¡4.3 mm 2 for Aaw, and ¡11.2 mm 3 for Vi with no systematic error. Morphometric measurements agreed with micro-CT (¡2.5 mm 2 ) without systematic error.In conclusion, micro-computed tomography image data from inflation-fixed airways can be used as calibration standards for three-dimensional lumen volume measurements from high-resolution computed tomography, while morphometry is acceptable for two-dimensional measurements. The image dataset could be used to validate other developmental three-dimensional segmentation algorithms.

We found clear evidence of differences in airway behaviour in the asthmatic group. Asthmatic airways were narrower at baseline and responded to inhaled methacholine by more heterogeneous narrowing of parallel sister airways and greater airway closure.