B35-06 Anti-MPO Positive Severe Asthma: A Diagnostic Intersection Between Asthma and ANCA-associated Vasculitis

Abstract Introduction Asthma with nasal polyposis is classically linked to type 2 inflammation and eosinophilia. However, anti-myeloperoxidase (MPO) antibody positivity without eosinophilia introduces a diagnostic dilemma that overlaps with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Recognizing this non-eosinophilic, autoimmune airway phenotype is essential for guiding precision therapy. Case Description A 40-year-old woman with severe persistent asthma on high-dose inhaled corticosteroid/long-acting β-agonist therapy presented for follow-up due to recurrent wheezing and nasal congestion. Comorbidities included obstructive sleep apnea and hypertension. She used her rescue inhaler three to four times weekly and nebulized bronchodilator three times monthly, with symptoms triggered by heat, dust, and pet dander. Examination revealed nasal polyps, periorbital hyperpigmentation, and diffuse expiratory wheezing. Laboratory studies showed positive anti-MPO antibody with a normal peripheral eosinophil count. High-resolution chest computed tomography demonstrated peribronchiolar ground-glass opacities in the right middle lobe, consistent with inflammatory bronchiolitis. There was no renal, neurologic, or dermatologic involvement. Given persistent respiratory symptoms and discordant laboratory findings, rheumatology and pulmonology were jointly consulted. The presentation was considered airway-limited ANCA-associated small-vessel disease versus non-eosinophilic severe asthma. A course of systemic corticosteroids was initiated with gradual taper, followed by methotrexate for steroid-sparing maintenance. The patient’s symptoms improved with reduced wheezing and decreased use of rescue inhaler therapy. Discussion This case illustrates an unusual overlap between severe asthma and ANCA-associated airway disease. Although MPO-ANCA is typically associated with interstitial or systemic vasculitis, airway-predominant forms such as bronchiolitis are increasingly recognized. The coexistence of nasal polyps and asthma with MPO-ANCA positivity but normal eosinophils represents a discordant clinical pattern that should prompt evaluation for autoimmune airway inflammation rather than isolated asthma.This presentation highlights the importance of reconsidering the diagnosis when clinical features diverge from expected inflammatory profiles. Distinguishing type 2 asthma from ANCA-mediated small-airway disease has major therapeutic implications, as immunosuppressive regimens rather than biologic agents may be indicated. Close collaboration between pulmonology and rheumatology with serial monitoring is essential to detect systemic evolution of vasculitis and ensure timely adjustment of therapy. This abstract is funded by: None