Background: FeNO is a well-known biomarker of type 2 inflammation and is widely used for patient phenotyping in severe asthma (SA). Few evidence is available on the value of multiple flows FeNO parameters on this topic.

Aims: the study aims to investigate the role of alveolar nitric oxide concentration (CaNO) and maximum conducting airway wall flux (J'awNO) in a cohort of patients with SA treated with biologic drugs.

Methods: We retrospectively collected clinical, demographic and respiratory functional data of SA patients whose multiple-flows FeNO analysis has been performed at baseline and after one year of biologic treatment (t0 and t1, respectively). Patients were classified into three groups (allergic, eosinophilic, mixed) according to SA endotype.

Results:we enrolled 47 patients with SA, of which 14 with allergic SA, 14 with eosinophilic SA and 19 with mixed allergic-eosinophilic SA. At t0, allergic patients showed lower serum eosinophils (p=0.0005), lower FeNO and J?awNO values (both p<0.0001) than the other subgroups; no differences were found in serum IgE, CaNO, exacerbation rate and FEV1. At t1, we observed a significant reduction of FeNO, J?awNO and CaNO levels only in eosinophilic and mixed subgroups. Good responders showed a more pronounced decrease of FeNO and J?awNO than partial/bad responders (p=0.032 and p=0.002, respectively). Delta (t1-t0) J?awNO showed the best accuracy in predicting a good response to treatment (area under the curve: 0.857, p=0.005).

Conclusions: J?awNO was differently expressed among the SA endotypes and showed a better accuracy than FeNO in predicting a good response to biologic treatment, supporting its potential use in clinical practice.