Abstract
<h3>Introduction</h3> We describe two severe asthmatics on opposite ends of the Type 2 inflammatory spectrum. One patient with high Type 2 signature including AERD. The other with low Type 2 inflammation with CVID and infection-driven asthma. Both experienced significant improvement of upper and lower respiratory symptoms with tezepelumab. <h3>Case Description</h3> A 46-year-old male AERD patient suffered from severe asthma and nasal polyposis with anosmia. His symptoms persisted despite high-dose inhaled corticosteroid/long-acting beta<sub>2</sub>-agonist, systemic corticosteroids, budesonide saline sinus rinses, and multiple nasal polypectomies, causing a significant impact on QoL. Three months post-tezepelumab treatment resulted in 1,000 mL increase in FEV<sub>1</sub>. He no longer needed systemic corticosteroids or use of his rescue inhaler. Anosmia resolved and taste returned. A 14-year-old female CVID patient with low peripheral eosinophil count, low total IgE, allergen skin test negativity, and low FeNO had poorly controlled asthma despite subcutaneous immunoglobulin therapy. Three months post-tezepelumab, her spirometry values normalized for the first time in years. Her FEV<sub>1</sub> increased by 500 mL. After tezepelumab, she was able to resume competitive sports without symptoms, no longer required corticosteroid bursts, and rare rescue inhaler use. <h3>Discussion</h3> These cases illustrate tezepelumab's ubiquitous efficacy of treating respiratory symptoms ranging from AERD to CVID. TSLP released from epithelial barrier disruptions may be a commonality across asthma endotypes. This provides insight about the unified airway and creates exciting new possibilities for the treatment of both Type 2 and non-Type 2 respiratory diseases.
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