Diagnostic and Therapeutic Challenges in Asthma and Chronic Obstructive Pulmonary Disease Overlap: A Four-Patient Case Series.

Asthma-chronic obstructive pulmonary disease (COPD) overlap is a heterogeneous clinical descriptor applied to patients with persistent airflow limitation who exhibit features of both asthma and chronic obstructive pulmonary disease. Diagnostic uncertainty is common, particularly when smoking-related emphysema coexists with asthma-associated traits such as bronchodilator reversibility, allergic rhinitis or atopy, eosinophilia, and elevated immunoglobulin E. We report four adults with chronic obstructive physiology and overlapping clinical, radiographic, physiologic, and inflammatory features. Two patients had persistent symptoms despite guideline-directed inhaled therapy and were treated with add-on biologic therapy targeting type 2 inflammation using benralizumab or dupilumab. The dupilumab-treated case demonstrated symptomatic and spirometric improvement over three months, whereas the benralizumab-treated case illustrates phenotype-guided biologic selection in eosinophilic asthma with coexisting COPD features and persistent severe obstruction on verified follow-up spirometry. The remaining cases illustrate practical diagnostic challenges, including the interpretation of serial spirometry, the recognition of bronchodilator responsiveness, and the reconciliation of radiographic emphysema with asthma-like variability and allergic sensitization. This case series highlights the clinical heterogeneity of asthma-chronic obstructive pulmonary disease overlap and supports a phenotype-informed approach incorporating spirometry, imaging, allergic evaluation, and accessible type 2 inflammatory biomarkers. Further prospective studies are needed to define which overlap phenotypes are most likely to benefit from biologic therapy.