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The effect of conductive ventilation heterogeneity on diffusing capacity measurement

¹Respiratory Division, University Hospital (Universitair Ziekenhusi Brussel), Vrije Universiteit Brussel, Brussels, Belgium; ²Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Victoria, Australia

Submitted 28 August 2007 ; accepted in final form 13 February 2008

It has long been assumed that the ventilation heterogeneity associated with lung disease could, in itself, affect the measurement of carbon monoxide transfer factor. The aim of this study was to investigate the potential estimation errors of carbon monoxide diffusing capacity (DL_CO) measurement that are specifically due to conductive ventilation heterogeneity, i.e., due to a combination of ventilation heterogeneity and flow asynchrony between lung units larger than acini. We induced conductive airway ventilation heterogeneity in 35 never-smoker normal subjects by histamine provocation and related the resulting changes in conductive ventilation heterogeneity (derived from the multiple-breath washout test) to corresponding changes in diffusing capacity, alveolar volume, and inspired vital capacity (derived from the single-breath DL_CO method). Average conductive ventilation heterogeneity doubled (P < 0.001), whereas DL_CO decreased by 6% (P < 0.001), with no correlation between individual data (P > 0.1). Average inspired vital capacity and alveolar volume both decreased significantly by, respectively, 6 and 3%, and the individual changes in alveolar volume and in conductive ventilation heterogeneity were correlated (r = –0.46; P = 0.006). These findings can be brought in agreement with recent modeling work, where specific ventilation heterogeneity resulting from different distributions of either inspired volume or end-expiratory lung volume have been shown to affect DL_CO estimation errors in opposite ways. Even in the presence of flow asynchrony, these errors appear to largely cancel out in our experimental situation of histamine-induced conductive ventilation heterogeneity. Finally, we also predicted which alternative combination of specific ventilation heterogeneity and flow asynchrony could affect DL_CO estimate in a more substantial fashion in diseased lungs, irrespective of any diffusion-dependent effects.

histamine; ventilation maldistribution