Longitudinal changes in sputum and blood inflammatory mediators during FeNO suppression testing

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 D2 (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.

Modelling ASthma TrEatment Responses (MASTER): Effect of individual patient characteristics on the risk of exacerbation in moderate or severe asthma: A time‐to‐event analysis of randomized clinical trials

“…It should be noted that our analysis excluded some factors that were identified as predictors or risk factors for exacerbation in previous reports, such as race (ethnicity), longer duration of symptoms, or geographic region, as these factors may be confounded by correlations (e.g., collinearity) or described by a different hierarchical relationship (e.g., seasonal variation and geographic region) 39,40 . In addition, we had very limited information on type‐2 biomarkers, now known to be associated with the risk of exacerbations and the likelihood of a positive response to corticosteroids or biologics in severe asthma 41 . Interestingly, previous investigations have also indicated maintenance corticosteroid use as a predictor of asthma exacerbation, but have not disentangled it from the effect of individual baseline characteristics.…”

Effectiveness of FeNO‐guided treatment in adult asthma patients: A systematic review and meta‐analysis

“…For the same reason, we believe that FeNO should ideally not be used as a standalone test to make treatment decisions, but should be combined with other simple measures of asthma control (e.g., ACQ), as most studies did. Whether addition of other noninvasive markers of asthma control that are mechanistically complimentary, such as blood eosinophils, can further improve outcomes is mostly unclear 28,34,35 …”

“…Whether addition of other noninvasive markers of asthma control that are mechanistically complimentary, such as blood eosinophils, can further improve outcomes is mostly unclear. 28,34,35 Over the past years, treatment with biologicals affecting the airway inflammatory pathways involved in asthma has rapidly emerged.…”

“…7 In addition, large numbers of studies have evaluated a potential role of FeNO in asthma care, not only for treatment selection, but also for, for example, diagnosis of (eosinophilic) asthma, prediction of asthma outcomes and assessing adherence to treatm ent. [7][8][9][10]34,35,[38][39][40] Although FeNO has been implemented in clinical practice in many healthcare centres worldwide, discussion regarding the added value for most of these indications remains. 7,8 Our findings provide new evidence to this discussion.…”

Challenges in severe asthma: Do we need new drugs or new biomarkers?

“…A recent observational study evaluated the correlation between FeNO suppression after high-intensity corticosteroid therapy, asthma control, and sputum eosinophilia ( 53 ). They reported that persistently elevated FeNO despite corticosteroid therapy was associated with persistent sputum eosinophilia and worse control.…”