Advances in biologic therapies for COPD: precision medicine approaches and implications for small-airway disease

COPD is a progressive respiratory condition marked by persistent airflow limitation and chronic inflammation, mainly caused by cigarette smoking. Although current inhaled therapies improve symptoms and reduce exacerbations, they do not substantially modify disease progression, emphasizing the need for novel therapeutic approaches.

This review provides a comprehensive overview of the effectiveness and mechanisms of biologic therapies in the management of COPD. We discuss the mechanistic rationale, clinical efficacy, and limitations of currently approved and emerging biologics, highlighting their relevance to distinct inflammatory endotypes of COPD. The role of small-airway disease in COPD is highlighted, together with advances in drug formulation and inhaled delivery technologies. Challenges related to drug delivery, particularly the influence of particle size on distal airway deposition, are examined, along with recent innovations in nanotechnology and comparative considerations of systemic versus inhaled therapeutic approaches. Relevant literature was identified through searches of PubMed (MEDLINE), Embase, Web of Science, and Google Scholar. Studies available in print or online up to June 2025 were considered.

Biologic therapies offer promise for selected COPD phenotypes; however, their long-term impact will depend on precision medicine, optimized airway-targeted delivery, and integration with established inhaled treatments to achieve meaningful disease modification.