Importance of Type and Degree of IgE Sensitisation for Defining Fractional Exhaled Nitric Oxide Reference Values

Background: Fractional exhaled nitric oxide (FENO) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FENO and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FENO levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation. Methods: FENO was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdio-Pulmonary bioImage Study (SCAPIS). Atopic subjects (n = 424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop (TM), >= 0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n = 1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles: (T1<1.16, T2 1.16-3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens. Results: Subjects IgE-sensitised to cat or mite had higher FENO compared to non-atopic subjects (FENO (ppb): median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p < 0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p = 0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop: >3.72 PAU/l) had the highest FENO compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p < 0.001). Conclusions: The type and degree of IgE sensitisation should be considered in generating FENO reference values.