Eosinophil-linked pulmonary circulation in EGPA Improves under anti-IL-5/R therapy: A longitudinal study

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by eosinophilic inflammation and potential cardiovascular involvement. The relationship between eosinophil burden and subclinical cardiopulmonary vascular dysfunction remains unclear. METHODS: 27 EGPA patients were evaluated. Peripheral eosinophil counts (PEC) at diagnosis were analysed in relation to echocardiographic markers of pulmonary vascular load and right ventricular-pulmonary artery (RV-PA) coupling. Patients initiating anti-IL-5/R therapy (mepolizumab or benralizumab) underwent echocardiography assessing pulmonary artery systolic pressure (PAPs), tricuspid annular plane systolic excursion (TAPSE), TAPSE/PAPs ratio, and tricuspid regurgitation velocity (TRV) at diagnosis, treatment initiation (Baseline), and 24-month follow-up (T24) to assess temporal changes. Patients were stratified by median PEC. Multivariable regression and ROC analyses were performed. RESULTS: At Baseline, 33% of patients exhibited elevated PAPs (>25 mmHg) despite absence of clinical pulmonary hypertension. Higher PEC were associated with increased PAPs (p = 0.04) and reduced TAPSE/PAPs ratio (p = 0.03). Pulmonary vascular load worsened from diagnosis to T0 and improved after anti-IL-5/R therapy, with PAPs decreasing from 27.5 [18.0-30.0] mmHg to 18.0 [11.75-20.0] mmHg (p = 0.002) and TRV from 2.30 [1.65-2.48] to 1.80 [1.28-1.92] m/s (p = 0.005). Baseline PEC moderately discriminated patients with intermediate/high echocardiographic probability of pulmonary hypertension (AUC 0.751). CONCLUSION: Elevated PEC may signal early pulmonary vascular dysfunction and RV-PA uncoupling EGPA, which may be partially reverted with anti-IL-5/R therapy. These findings support the importance of early cardiovascular surveillance in eosinophil-rich EGPA.