Background: Eosinophil-derived neurotoxin (EDN) reflects eosinophil activation in asthma and may provide added value to characterize type 2 inflammation in asthma. More research is needed regarding normal ranges and determinants of EDN in order to enable its clinical use.

Aim: We aimed to study respiratory determinants of EDN in the general population using the Swedish CArdioPulmonary bioImage Study (SCAPIS) and propose reference values for EDN, including the upper limit of normal (ULN), defined as 95th percentile, in a healthy sub-population. 

Methods: We used 4916 subjects (age 50-64 yrs) from the SCAPIS Uppsala cohort to assess EDN in relation to age, gender, lifestyle and clinical conditions using univariate and multivariate analyses. To define normal values of EDN, we selected a healthy sub-population (reference population) of subjects free from EDN-modifying conditions (256 men and 456 women).

Results: Male gender, BMI>25 kg/m², atopy and current smoking were associated with higher EDN levels (all p-values<0.003). Asthma, allergic rhinitis and airways obstruction were also associated with higher EDN (all p-values <=0.003). Having asthma or allergic rhinitis or airways obstruction related to 10-11% higher EDN levels in adjusted regression models. Median and ULN values of EDN in the reference population were 21.9 ng/ml and 68.6 ng/ml, respectively, for men, and 19.1 ng/ml and 44.1 ng/ml, respectively, for women. 

Conclusion: Many individual related factors are associated with high EDN values that should be considered for EDN interpretation. The proposed EDN reference values offer an interpretation frame that needs to be validated in further studies with broader age ranges.