Abstract Introduction E-cigarette or vaping-associated lung injury (EVALI) remains a heterogeneous and clinically challenging entity characterized by acute or subacute lung injury following recent vaping exposure. Although corticosteroids constitute standard therapy, management becomes particularly complex in solid organ transplant recipients, in whom prolonged high-dose glucocorticoids may exacerbate infectious risk and chronic allograft dysfunction. Eosinophilic EVALI represents a rare phenotype defined by prominent alveolar and peripheral eosinophilia and histopathologic features resembling acute eosinophilic pneumonia. Interleukin-5 (IL-5) pathway blockade has demonstrated efficacy in eosinophilic asthma and hypereosinophilic syndromes, yet has not been extensively evaluated in transplant-associated eosinophilic lung injury. Case Presentation A 34-year-old woman with cystic fibrosis status post bilateral lung transplantation (104 weeks post-transplant), end-stage renal disease on dialysis, and CF-related diabetes presented with acute hypoxemic respiratory failure following continued vaping of tetrahydrocannabinol products. Chest computed tomography demonstrated diffuse bilateral ground-glass opacities. Infectious work-up, including extensive bacterial, viral, fungal, and parasitic testing, was negative. Bronchoalveolar lavage revealed 25% eosinophils and peripheral eosinophilia (absolute eosinophil count 1,092/μL). Despite two weeks of high-dose IV methylprednisolone, respiratory failure progressed to ARDS. Given refractory eosinophilic lung injury in the setting of significant immunosuppression, a single dose of benralizumab was administered. Within two weeks, the patient demonstrated marked clinical improvement, recovery of oxygenation, dramatic radiographic resolution, and near-complete depletion of eosinophils (BAL eosinophils decreased to 2% by day 20; peripheral counts normalized). Discussion This case highlights targeted IL-5 receptor inhibition as a rational immunomodulatory strategy for steroid-refractory eosinophilic EVALI in a lung transplant recipient. In this unique immunologic milieu, benralizumab facilitated rapid eosinophil depletion and clinical improvement, without the need for prolonged corticosteroid exposure. Mechanistically, benralizumab promotes antibody-dependent cell-mediated cytotoxicity by binding to the IL-5 receptor alpha, thereby rapidly eliminating eosinophils and eosinophil precursors. The potential steroid-sparing effect is particularly relevant in transplant populations at high risk for infection, metabolic complications, and allograft dysfunction. Targeted IL-5 pathway blockade may serve as effective rescue therapy for severe eosinophilic EVALI unresponsive to corticosteroids in lung transplant recipients. This case highlights the importance of further research on selective eosinophil-directed biologics in post-transplant inflammatory lung diseases, where minimizing systemic immunosuppression remains crucial. This abstract is funded by: None
Sanchez et al. (Fri,) studied this question.