Association Between Neutrophil Extracellular Traps in Bronchoalveolar Lavage Fluid and Severity of Drug-Induced Lung Injury

Neutrophil extracellular traps (NETs) play a pivotal role in early immune responses and are implicated in various respiratory diseases, such as acute respiratory distress syndrome (ARDS). A correlation between NETs in bronchoalveolar lavage fluid (BALF) and the severity of ARDS has been reported. NETs are also associated with drug-induced organ disorders. However, the relationship between drug-induced lung injury (DLI) and NETs remains unclear. This study aimed to establish and substantiate this relationship. We conducted a retrospective observational study. We extracted DLI cases in which BAL was performed at Tottori university hospital. Based on the need for glucocorticoid treatment, patients were classified into the "moderate severity or above" group (PaO2 < 80 mmHg) and "mild" group (PaO2 ≧ 80 mmHg). We examined myeloperoxidase, neutrophil elastase, and double-strand-DNA levels in BALFs, and examined their association with clinical findings and severity, with non-parametric Mann-Whitney U test. We studied 46 patients with DLI. The "moderate severity or above" group had 32 patients, while the "mild" group had 14 patients, and NETs in BALF were significantly higher in the former group. Three cases showed a diffuse alveolar damage (DAD) pattern on high-resolution computed tomography (HRCT), with significantly higher NET levels that those with non-DAD patterns. In DLI, NETs in BALF were found to be related with disease severity and the presence of DAD patterns in HRCT images. Measuring NETs in BALF offer potential utility in guiding future treatment selection and aiding the differential diagnosis of clinical phenotypes.