Looking for new biomarkers in bronchiectasis (BE): sputum Alpha1 antitrypsine (AAT), Neutrophil Elastase activity (NE) and secretory leucocyte protease inhibitor (SLPI).

<bold>Introduction:</bold> In the age of precision medicine, biomarkers and therapeutic targets play a fundamental role. The aim of our study is to describe the role of some key proteases and antiproteases in BE airways and their potential as BE biomarkers. <bold>Methods:</bold> We collected spontaneous sputum, blood and clinical data from stable BE patients. AAT, SLPI, and NE levels were measured in sputum supernatant using ELISA. Also, AAT was measured in blood with nephelometry to calculate the sputum-to-blood ratio (SBAAT). <bold>Results:</bold> We included 76 patients, 70% women, mean age 61±16, mean FEV1 84.6±25.5%; 31% moderate and 20% severe according to FACED scores. NE had inverse correlation with FEV1 (liters r=-0.278,p=0.030; FEV1%, r=-0.399,p=0.001), FVC% (r=-0.398, p=0.002) and positive correlation with Pseudomonas aeruginosa (PA) infection (r=0.340; p=0.007) and severity (mild vs severe FACED, r=3.50,p=0.035). In contrast, SLPI had positive correlation with FEV1% (r=0.340,p=0.009) and cystic BE (p=0.007), negative correlation with PA (r=0.340; p=0.007) and FACED (mild vs severe, r=3.50,p=0.035). Consistently, negative correlation was found between NE and SLPI (r=-454;p<0.001). AAT levels in blood and sputum did not correlate with clinical, functional or radiological variables, nor with the other biomarkers but a higher SBAAT was found in higher Reiff scores (>6; p<0.001). <bold>Conclusions:</bold> Increased NE and reduced SLPI in BE patients are associated with worse lung function, severity, and chronic PA, marking them as potential biomarkers for disease activity. Patients with greater radiological impairment exhibit an elevated sputum-to-blood AAT gradient.