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Biomarkers of Therapeutic Response in Patients with Chronic Obstructive Pulmonary Disease

A Critical Review of the Literature

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Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality across the world. Unfortunately, none of the current therapies, except for smoking cessation and supplemental domiciliary oxygen for hypoxaemic patients, can modify its natural course or alter survival. The pipeline for new compounds is not very promising owing to repeated failures, and many large pharmaceutical companies have abandoned COPD drug discovery altogether. One major barrier to new drug discovery is the lack of modifiable biomarkers that can be used as surrogates of clinical outcomes such as exacerbation and mortality. The only accepted marker in COPD is forced expiratory volume in 1 second (FEV1). However, by definition, COPD is a non-reversible or poorly reversible condition with respect to FEV1. Thus, very few drugs except for bronchodilators have been able to address this endpoint. Of many candidate molecules, sputum neutrophil counts, exhaled corrected alveolar nitric oxide and proline-glycine-proline (PGP) and N-α-PGP, which are breakdown products of collagen, are promising lung-based biomarkers. However, their clinical utility has not been validated in large clinical trials. Promising blood biomarkers include surfactant protein D, and pulmonary- and activation-regulated chemokine (PARC/CCL-18). However, the clinical data have been inconsistent. Non-specific inflammatory biomarkers such as C-reactive protein and interleukin-6 lack specificity for COPD and thus are of limited clinical usefulness.

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Acknowledgements

No sources of funding were used in the preparation of this review. Dr Sin has received honoraria for speaking engagements and grant funding from AstraZeneca and GlaxoSmithKline. Dr Yoon has no conflicts of interest to declare.

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Authors and Affiliations

  1. UBC James Hogg Research Center, The Providence Heart and Lung Institute, St. Paul’s Hospital, 1081 Burrard Building, Vancouver, BC V6Z 1Y6, Canada

    Ho Il Yoon &  Don D. Sin

  2. Department of Internal Medicine and Lung Institute, Division of Respiratory and Critical Care Medicine, Seoul National University Bundang Hospital, Bundang, Korea

    Ho Il Yoon

  3. Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada

    Don D. Sin

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  1. Ho Il Yoon
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Correspondence to Don D. Sin.

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Yoon, H.I., Sin, D.D. Biomarkers of Therapeutic Response in Patients with Chronic Obstructive Pulmonary Disease. Drugs 71, 1821–1837 (2011). https://doi.org/10.2165/11595180-000000000-00000

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