Longitudinal changes in sputum and blood inflammatory mediators during FeNO suppression testing
Simon Couillard, Rahul Shrimanker, Samuel Lemaire‐Paquette, Gareth Hynes, Catherine Borg, Clare Connolly, Samantha Thulborn, Angela Moran, Sarah Poole, Sophie Morgan, Timothy J. Powell, Ian Pavord, Timothy Hinks
Abstract
To explore whether fractional exhaled nitric oxide (FeNO) non-suppression identifies corticosteroid resistance, we analysed inflammatory mediator changes during a FeNO suppression test with monitored high-intensity corticosteroid therapy. In linear mixed-effects models analysed over time, the 15 clinically distinct ‘suppressors’ (ie, ≥ 42% FeNO suppression) normalised Asthma Control Questionnaire scores (mean±SD, start to end of test: 2.8±1.4 to 1.4±0.9, p<0.0001) and sputum eosinophil counts (median (IQR), start to end of test: 29% (6%–41%) to 1% (1%–5%), p=0.0003) while significantly decreasing sputum prostaglandin D 2 (254 (89–894) to 93 (49–209) pg/mL, p=0.004) and numerically decreasing other type-2 cytokine, chemokine and alarmin levels. In comparison, the 19 non-suppressors had persistent sputum eosinophilia (10% (1%–67%) despite high-intensity therapy) with raised end-test inflammatory mediator levels (1.9 (0.9–2.8)-fold greater than suppressors). FeNO non-suppression during monitored treatment implies biological corticosteroid resistance.