Asthma is characterised by heterogeneous ventilation as measured by 3-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting beta agonist (ICS/LABA) treatment response is variable in asthma and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma.
Twenty-two symptomatic asthmatic participants underwent Single-Photon Emission Computed Tomography (SPECT)/CT imaging with Technegas, before and after 8-week fluticasone/formoterol (1000/40µg/day) treatment. Lung regions that were non-ventilated, low-ventilated or well-ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airway function (Sacin and Scond, respectively). Forced Oscillation Technique (FOT) was used to measure respiratory system resistance and reactance.
At baseline and post treatment Scond z-score was related to % non-ventilated lung, while Sacin z-score was related to % low-ventilated lung. Although symptoms, spirometry, FOT and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide-range of change in SPECT ventilation such that greater % non-ventilated lung, older age, and higher Scond, predicted a reduction in non-ventilated lung after treatment.
SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable with improvement occurring when small airway dysfunction and ventilation defects are more severe. Persistent ventilation defects which correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodelling underlie these defects.

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