INTRODUCTION. Two major groups of asthma phenotypes have been defined: T2-high (isolated
eosinophilia: EOS) and T2-low asthma. The latter is related to isolated neutrophilic, paucigranulocytic or mixed (both eosinophils and neutrophils) inflammation.

AIMS AND OBJECTIVES. This study aims to evaluate alarmins expression in mixed asthma.

METHODS. We have selected bronchial biopsies obtained from mild-to-severe asthmatics (n=52) and
divided them into MIXED (n=28, neutrophil count ?47.17 cells/mm² and eosinophil count >12.45 cells/mm²) and EOS (n=24). MIXED group has been further divided into intermediate (n=13, int-MIXED, neutrophil count >47.17 and <94.34 cells/mm²), and high (n=15, hi-MIXED, neutrophil count ?94.34 cells/mm²). Through immunohistochemistry we assessed the expression of the alarmins IL-25, IL-33, and TSLP in the bronchial mucosa of asthmatic patients. We then collected clinical and functional data.

RESULTS. We found that EOS had a higher percentage of past smoker than MIXED, while hi-MIXED patients showed a greater percentage of atopy and number of frequent exacerbations (OCS bursts) than EOS. No differences were found in the alarmins expression between EOS and MIXED. However, after stratifying the two groups in mild vs severe and exacerbators (exa, ?2/year) vs non-exacerbators (non-exa) we observed higher expression of TSLP in severe-MIXED than mild-MIXED and in exa-MIXED than non-exa-MIXED (p<0.05). Moreover, TSLP expression correlated positively with ICS dose, and negatively with pre- and post-BD FEV₁.

CONCLUSION. Our results pointed out the involvement of TSLP in mixed neutrophilic and eosinophilic
asthma characterized by high severity and frequent exacerbations.