Abstract Rationale Blood eosinophil count (BEC) and fractional exhaled nitric oxide (FENO), two major type-2 (T2) inflammatory markers, are associated with exacerbations, asthma morbidity, oral corticosteroids use, and lung function decline. However, BEC and FENO levels may reflect different T2 pathways and their associations with asthma characteristics in unselected populations remain unclear. We examined how BEC and FENO, independently and synergistically, are related to lung function, allergy, and nasal polyps in a population-based asthma cohort. Methods Data were analyzed from 1,567 participants with physician diagnosed asthma in the West Sweden Asthma Study. Lung function, bronchodilator responsiveness, and presence of allergy and nasal polyps were evaluated across categories of BEC (≤150, 150-300, 300 cell/μL) and FENO (≤20, 20-50, 50 ppb). Associations were assessed using generalized regression models adjusting for age, sex, BMI, and smoking. Results BEC was associated with nasal polyps independently of FENO. BEC and FENO interacted, showing a synergistic association in relation to allergy and lung function parameters except for pre-bronchodilator FEV₁. Despite its interaction with BEC, FENO on its own showed significant associations with pre-bronchodilator FEV₁/FVC (Figure 1). When current smokers were excluded, BEC was not independently associated with any outcome, and interacted in their association in with allergy and lung function parameters (FEV1, FVC, and FEV1/FVC). Similar results were observed among those with current ICS use. However, despite its interaction with FENO, BEC on its own showed significant associations with pre-bronchodilator FEV₁and FVC (%predicted), suggesting that BEC had a stronger relationship with these outcomes than FENO among ICS users. Conclusions BEC and FENO have three types of associations with lung function, allergy and nasal polyps: (a) Single strong independent marker: One marker is associated without interaction or the association of the other (BEC with nasal polyps). (b) Strong marker with interaction from the other: One marker is associated, but the association depends on interaction with the other (FENO with pre-bronchodilator FEV1/FVC). (c) Both strong interactive markers: BEC and FENO are strongly associated, and their associations synergistically depend on each other (pre- and post-bronchodilator FVC % predicted, allergic sensitization, and clinical allergy). Cigarette smoking and ICS use highly impacted the interaction and the association of both markers. Hence, BEC and FENO reflect distinct yet complementary aspects of T2-inflammation in asthma. These findings support the joint use of BEC and FENO for asthma phenotyping. This abstract is funded by: The study was supported by the VBG Group Herman Krefting Foundation for Asthma and Allergy Research (Trollhättan, Sweden), Swedish Research Council (Stockholm, Sweden), the Swedish Heart-Lung Foundation (Stockholm, Sweden), the Swedish Asthma and Allergy Foundation (Stockholm, Sweden), Tampere Tuberculosis Foundation (Tampere, Finland), and ALF agreement (grant from the Swedish state under the agreement between the Swedish Government and the county councils, Sweden).
Abohalaka et al. (Fri,) studied this question.