Non-type 2 asthma represents about 20-30% of all severe asthmatics. At the present time, there is no specific biomaker that may identify this specific endotype, apart from the absence of type 2 eosinophilic inflammation.; probably, in the next future we would have different biomarkers able to distinguish different subgroups in this large cohort of asthmatic subjects. This endotype may be frequently associated with some comorbidities, like obesity, gastroesophageal reflux of smoking habit). Noneosinophilic severe asthmatics not adequately controlled with the best of the standard therapy may require the addition of other drugs (tiotropium as first additional option, oral theophylline, or long-term macrolide therapy or PDE4 inhibitors). These patients usually respond poorly to oral corticosteroids, but, in any case, this treatment is often used by the majority of the patients, for the lack of significant and effective alternatives.

•Know how to diagnose this subgroup of severe asthmatics.

• Know the pathogenetic mechanisms of this specific endotype.

• Select the appropriate treatment and management of these “difficult-to-treat” patients.