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Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities  

Nature Reviews Drug Discovery (2025)Cite this article

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Abstract

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder of the lungs that affects about 10% of the adult population and is currently the third leading global cause of death. COPD is the result of multiple, repeated and dynamic gene–environment interactions, starting early in life, that determine the lung function trajectory that a given individual follows over a lifetime. Increasing understanding of COPD pathogenesis has opened many new opportunities for drug development, including recently approved monoclonal antibodies that reduce inflammatory cytokine signalling by targeting the IL-4α receptor or the eosinophil-activating IL-5. Drugs targeting a range of other culprits involved in COPD, including neutrophils, alarmins and kinases, are also in clinical development. As the current pipeline of drugs in development for COPD matures, potential areas for novel therapies continue to emerge while lessons from ongoing trials such as patient stratification can be used to refine the design of future trials in this disease.

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Fig. 1: Potential lung-function trajectories from childhood to old age.
Fig. 2: Overview of the inflammation network in COPD.
Fig. 3: Pharmacological targets of drugs currently or recently in COPD clinical trials.

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Acknowledgements

The authors thank A. Higham (University of Manchester, UK) for drawing the original Figures 2 and 3. D.S. is supported by the National Institute of Health Research (NIHR) Manchester Biomedical Research Centre, and R.F. by the Serra Hunter and ICREA Programs, Department de Universitats de la Generalitat de Catalunya. This work was supported by Instituto de Salud Carlos III (PMP21/00090), co-funded by the European Union (NextGenerationEU/Mecanismo para la Recuperación y la Resilencia (MRR)/PRTR).

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Authors and Affiliations

  1. Respiratory Institute, Clinic Barcelona, Barcelona, Spain

    Alvar Agusti

  2. Universitat de Barcelona, Barcelona, Spain

    Alvar Agusti & Rosa Faner

  3. Fundació Clinic-Institut d’Investigacions Biomédiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Spain

    Alvar Agusti & Rosa Faner

  4. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Spain

    Alvar Agusti & Rosa Faner

  5. University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK

    Dave Singh

  6. Medicines Evaluation Unit, Manchester, UK

    Dave Singh

  7. ICREA - Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

    Rosa Faner

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Glossary

Bronchiectasis

Disease characterized by permanent enlargement of parts of the airways of the lung.

Dyspnoea

Shortness of breath.

Goblet cells

A type of epithelial cell in the airways the primary function of which is to secrete mucins onto the internal surface of the respiratory tract.

ILC2s

Group 2 innate lymphoid cells; a subset of innate immune cells that have key roles in barrier immunity, especially at mucosal surfaces such as the lungs, gut and skin.

Mucins

A family of high molecular weight glycosylated proteins secreted by lung epithelial cells.

Neutrophil serine proteases

Enzymes produced by neutrophils that cleave peptide bonds in proteins.

Polygenic risk score

A number that summarizes the estimated effect of many genetic variants on an individual’s risk of a disease.

Syndemic

The co-occurrence of diseases with shared mechanisms and risk factors that can help to explain the clustering of certain morbidities in chronic obstructive pulmonary disease.

Treatable traits

A clinical (phenotype) or biological (endotype) characteristic that contributes to the heterogeneity of chronic airway diseases.

Type 1 inflammation

(TH1-mediated response). A type of immune response characterized by the participation of T helper 1 (TH1) cells, cytotoxic T cells (CD8+), macrophages, natural killer cells and neutrophils. Key participating cytokines are interferon-γ, IL-2 and TNF.

Type 2 inflammation

(TH2-mediated response). A type of immune response characterized by the participation of T helper 2 (TH2) cells, eosinophils, mast cells, basophils and B cells. Key participating cytokines are IL-4, IL-5 and IL-13.

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Agusti, A., Singh, D. & Faner, R. Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities  . Nat Rev Drug Discov (2025). https://doi.org/10.1038/s41573-025-01290-6

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