• Granulomatosi eosinofila con Poliangite
• Asma Grave
• Ipereosinofilia

Background: Severe hypereosinophilic asthma (SEA) is the prodromal phase of EGPA, nevertheless there are no studies trying to recognize EGPA when the eosinophilic inflammation is still confined to upper and lower airway.
Aims: To identify a panel of biological, clinical and functional markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA.
Methods: 30 patients with EGPA and 49 with SEA who do not fulfilled the diagnostic criteria of EGPA were enrolled. All patients underwent to a pulmonary and ENT visit. EGPA patients received rheumatologic assessment. Lung function and methacholine test were performed. Blood biomarkers were assessed: eosinophils, eosinophilic cationic protein, interleukins: IL5-IL4, IGE, IgG4, ANCA and sputum biomarkers: eosinophils, periostin, IL8, GMCSF. The ACT test, short form (SF)-36, SinoNasal Outcome Test and the Asthma Quality of Life Questionnaire were also used.
Results: No differences were observed between SEA and EGPA patients in lung function but SEA patients had a worst asthma control (p<0.001). Patients with SEA presented higher level of sputum eosinophils (p<0.002) while EGPA patients had had higher level of blood eosinophils in the past. The GMCSF was the only biomarker significantly increased in EGPA patients compared with SEA; in a post-hoc analysis, SEA patients with some features of diagnostic criteria of EGPA presented significantly higher level of sputum GMCSF (p<0.000). IgG4 was abnormally increase in one SEA patient positive for ANCA but without systemic manifestation. 
Conclusion: Sputum GMCSF might be a good biomarker of systemic eosinophilic disease; ANCA and IgG4, considered together, may support the suspicious of EGPA in SEA.