NO production depth in the conducting airways in T2-high asthma

<bold>Aim:</bold> To present preliminary findings from a novel non-invasive method for estimating the site of nitric oxide(NO) production in the conducting airways. <bold>Method:</bold> Highly time-resolved measurements of fractional exhaled NO (FeNO) were made using a novel laser-absorption spectroscopy (LAS) sensor[1]. A personalized lung deadspace (PDS), estimated with Computed Cardiopulmonography (another LAS technique)[2], was used to simulate NO expirograms produced at different depths along the conducting airways to form a ‘wallpaper’ (series of coloured lines). The measured NO expirogram was superimposed on the wallpaper (dotted line), to estimate the patient’s NO production depth: H (% PDS) (Fig 1A&B). <bold>Results:</bold> We studied 7 treatment-naïve (TN) asthma patients (FeNO 88±52ppb, mean±SD) and 10 patients on GINA 4 high-dose inhaled corticosteroids (H-ICS) (FeNO 95±31ppb). The H-ICS group had a more distal NO production (H = 47.2±12.4% PDS) compared to the TN group (H = 33.3±10.7% PDS, p = 0.03) (Fig 1C). After 8 weeks of ICS therapy the TN group had a small non-significant rise in H of 5±7% PDS. <fig><object-id>erj;64/suppl_68/PA339/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <bold>Conclusion:</bold> NO appears to arise from deeper airways in more severe asthma, potentially reflecting effective targeting of proximal but not distal airways inflammation by ICS. This novel method could provide a valuable biomarker for the site of type-2 inflammation and the likely effectiveness of inhaled therapies. [1] 10.1088/1752-7163/ab9c31 [2] 10.1152/japplphysiol.00745.2017