Abstract Introduction Pulmonary alveolar proteinosis (PAP) is a rare disorder of surfactant accumulation caused by impaired macrophage clearance. It may occur as an autoimmune, secondary, or congenital disease. Autoimmune PAP is defined by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. Although inhalational exposures have been linked to secondary PAP, the interaction between E-Cigarette or vaping-associated lung injury (EVALI) and autoimmune PAP is not well understood. We present a case of acute hypoxemic respiratory failure where concurrent EVALI and autoimmune PAP created diagnostic and management challenges. Case Description A 65-year-old woman with chronic obstructive pulmonary disease (COPD), tobacco use, and recent vaping resumption (after a 7-year cessation) presented with one month of worsening dyspnea and cough. She had received two outpatient steroid courses and doxycycline without improvement. On admission, she was hypoxemic, requiring supplemental oxygen, febrile, and tachypneic. Laboratory testing showed leukocytosis (18,000 cells/µL) with negative procalcitonin, viral, and bacterial studies. CT chest demonstrated diffuse bilateral ground-glass opacities (Figure 1). Bronchoscopy with bronchoalveolar lavage (BAL) revealed 44 % neutrophils, 43 % macrophages, and negative cultures. Autoimmune and infectious workup (Figure 1) was unrevealing except for elevated anti-GM-CSF antibodies. The patient deteriorated despite corticosteroids, empiric antibiotics, and supportive measures, progressing to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Whole-lung lavage showed no characteristic milky effluent or PAS-positive material. Post-mortem lung histopathology revealed PAS-positive intra-alveolar proteinaceous material with foamy macrophages and diffuse alveolar damage, confirming autoimmune PAP overlapping with EVALI. Discussion PAP results from defective surfactant clearance and can mimic other causes of diffuse alveolar disease. While autoimmune PAP is associated with anti-GM-CSF antibodies, secondary forms arise from hematologic, autoimmune, or inhalational exposures. Smoking is reported in up to 79 % of PAP patients and is associated with poor response to whole-lung lavage. Vaping may augment pulmonary inflammation and disrupt surfactant metabolism through oxidative injury and cytokine release, including GM-CSF. Our case suggests vaping may unmask or exacerbate autoimmune PAP, leading to fulminant respiratory failure. Conclusion This case highlights the diagnostic complexity of PAP in the setting of inhalational injury. Coexisting vaping-related lung injury may obscure classical features and impair treatment response. Awareness of this overlap is essential to guide timely diagnosis and multidisciplinary management. Further studies are warranted to elucidate vaping’s impact on surfactant regulation and autoimmune mechanisms. This abstract is funded by: None
Seijari et al. (2026) studied this question.