D1.435 - Eosinophilic diseases: from nasal polyposis, eosinophilic asthma to EGPA (Eosinophilic Vasculitis with PolyAngioitis), evaluation of possible biomarkers of disease evolution

Eosinophilic granulomatosis with polyangiitis (EGPA) is one of a group of systemic diseases affecting small vessels and several areas as the respiratory system, kidneys, skin and more. It generally develops in three moments: a prodromal phase typical of high type 2 inflammation, always characterized by asthma and chronic rhinosinusitis with and without nasal polyposis; an often overlapping phase with hypereosinophilia, often related to end organ involvement; and finally a vasculitic phase, characterized by typical vascular manifestations of small vessels. The unsolved needs of patients with EGPA relate to the possibility of predicting vasculitic evolution compared to a prodromal phase which is characterized by hypereosinophilia and asthma in 90% of patients and also a comorbidity such as nasal polyposis. The need arises for the search for a shared biomarker that not only indicates the disease at the tissue level but also at the prodromal phase so to intercept the vasculitic phase and hopefully modify its natural history and treat it. Primary objectives of our observational, ambispective study are to describe the histological characteristics of nasal polyp in patients with nasal polyposis, nasal polyposis and eosinophilic asthma, EGPA. Secondary objectives are to characterize nasal microbiota in patients with nasal polyposis, nasal polyposis and eosinophilic asthma, EGPA; to evaluate the clinical characteristics and response to therapy in patients affected by EGPA compared to patients affected by isolated nasal polyposis or eosinophilic asthma and nasal polyposis, to evaluate the presence of staphylococcal enterotoxins as a biomarker of inflammation and barrier damage in the three patient cohorts and finally to evaluate the involvement of the peripheral nervous system in EGPA patients. 

We pre-screened 27 patients of which 11 with eosinophilic asthma and nasal polyps, 9 with EGPA and 7 with only nasal polyps with ipereosinophilia. We evaluated clinical and demografic characteristics of the population. We performed serum measurements of specific IgE against S. aureus enterotoxins using a fluorenzymatic immunoassay autoanalyzer. We performed nasal brushing to every patient and also a nasal polyps biopsy which will be examinated afterwards with GeoMx©, an assay that utilizes ISH probes linked to indexing oligo barcodes via a photocleavable linker and the GeoMx©. 

Of the 17 women and 10 men pre-screened median age was 55 years and median duration of disease was 5 years. The median Fev1 of patients was 73% of capacity function. The medium value of eosinophilia was 1430 mm3 at the baseline. The medium dose of corticosteroids was 15 mg/die. 54% of the study population was positive for Staphilococcus Aureus enterotoxins. The presence of Staphilococcus Aureus specific IgE is statistically related to ipereosinophilia (eosinophils>1000/mm3) while neurosensorial damage not. 30% of EGPA patients had neurosensorial damage. Nasal brushing and ECP (cationic eosinophilic protein) whose medium value was 84 μg/L (normal value of < 20 mg/L) were performed.

We are taking further steps to relate metabolomic data to serum markers since today in precision medicine the role of biomarkers in a disease that has a prodromal phase with variably long organ damage and subsequently systemic effects is of vital importance for clustering a patient endotype and if possible predicting the risk of developing the disease.