C33-29 Not All Cough in Alpha-1 Antitrypsin Deficiency Is Emphysema: A Case of Eosinophilic Asthma

Abstract Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder that predisposes to early-onset emphysema and bronchiectasis through protease-antiprotease imbalance and neutrophil-driven inflammation. Although asthma and atopy occur more frequently in AATD, eosinophilic asthma is rarely documented. This case highlights a patient with genetically confirmed severe AATD whose chronic cough stemmed not from emphysema, but from eosinophilic asthma. A 39-year-old nonsmoking woman with Raynaud’s disease and recurrent sinusitis presented with a two-year history of chronic cough and intermittent dyspnea. She had required multiple short courses of oral corticosteroids with transient relief. Spirometry was normal (FEV₁ 97% predicted, FEV₁/FVC 89%), and DLCO was preserved (85% predicted). High-resolution CT revealed mild lower-lobe bronchiectasis without emphysema. Serum alpha-1 antitrypsin was 25 mg/dL, and genotyping confirmed a homozygous ZZ mutation. Peripheral eosinophilia (1.5 × 109/L; 21%) and bronchoalveolar lavage showing 43% eosinophils confirmed type-2 airway inflammation. All bacterial and fungal cultures, including Aspergillus precipitins, were negative. She was treated with inhaled budesonide/formoterol for airway inflammation and intranasal ipratropium for postnasal-drip-related symptoms, with partial improvement. Persistent cough and elevated eosinophils prompted initiation of Mepolizumab 100 mg subcutaneously every 4 weeks per ATS/ERS severe-asthma guidance. Over three months she reported improved symptom control and reduced cough frequency, allowing consideration of inhaled corticosteroid step-down. Lung function remained normal. In the absence of emphysema or fixed obstruction, augmentation therapy for AATD was not indicated. Emphysema is the hallmark pulmonary manifestation of ZZ AATD, affecting most adults, whereas asthma occurs in a minority. This patient’s normal spirometry, preserved diffusion, and eosinophilic airway inflammation were consistent with eosinophilic asthma coexisting with but mechanistically distinct from AATD. The two processes represent different inflammatory pathways - neutrophilic tissue injury versus IL-5-driven eosinophilic inflammation - but can intersect clinically. Management should follow severe-asthma protocols, with high-dose inhaled corticosteroid-LABA therapy and biologic add-on (anti-IL-5 or anti-IL-4Rα) for persistent eosinophilia. The clinical response suggests that biologic therapy remains effective in the setting of AATD. Patients require dual monitoring: spirometry and DLCO for AATD progression, and eosinophil counts and symptom assessment for asthma control. Not every cough in AATD signals emphysema progression. Recognizing eosinophilic asthma as a coexisting, treatable inflammatory phenotype allows targeted therapy and improved control while maintaining vigilance for longterm AATD related complications. This abstract is funded by: None