• Chronic Obstructive Pulmonary Disease
• Pulmonary Genomics
• Smoking Cessation

Personalized medicine describes an individualized approach to treatment that takes into account the unique clinical, genetic, and molecular features of a disease for each patient. Blanca Camoretti-Mercado, PhD, University of Chicago, Chicago, Illinois, USA, described advances in the use of personalized medicine for patients with chronic obstructive pulmonary disease (COPD).

Effective management of COPD requires multidisciplinary care that may include smoking cessation, treatment with bronchodilators and glucocorticoids, oxygen therapy, pulmonary rehabilitation, and, in severe cases, surgical treatment with lung reduction or transplantation. Each of these components of therapy can be refined further according to individual patient factors. While few options for personalized medicine are available in current clinical practice, ongoing research on COPD susceptibility and pathogenesis has revealed potential therapeutic targets for specific subpopulations of patients with COPD.

Among smokers, certain single-nucleotide polymorphisms (SNPs) on chromosome 15, where the nicotinic receptor gene cluster resides, are associated with an increased risk of nicotine dependence and heavy smoking. One SNP, rs16969968, influences both nicotine dependence and the risk of lung cancer and COPD. In the future, this SNP may serve as a marker to identify smokers who need more intensive behavioral modification and pharmacological approaches to overcome nicotine dependence [Bierut LJ. Trends Pharmacol Sci 2010].

Alterations in the transforming growth factor (TGF)-beta signaling pathway have been implicated in the pathogenesis of COPD. Genetic differences that influence the expression of proteins along the TGF signaling pathway may have important implications for individualized COPD treatment. Most cells secrete TGF-beta as a complex that contains one of three latent TGF-beta binding proteins (Ltbp1, Ltbp3, and Ltbp4). Mutational inactivation of Ltbp4 causes defective TGF-beta signaling and an increased risk of the severe pulmonary emphysema phenotype of COPD. In a mouse model of COPD, mutational inactivation of the antioxidant protein sestrin 2 (sesn2) in Ltbp4-deficient mice reversed the emphysema phenotype. This suggests that patients with COPD that is due to altered TGF-beta signaling may benefit from treatment with antagonists of sestrin function [Wempe F et al. Dis Mod Mech 2010].

For patients with the emphysema phenotype of COPD, cell-based therapy is a promising option for restoring function to the pulmonary parenchyma. A recent proof-of-concept study examined the safety and efficacy of stem cell therapy in 4 patients with advanced COPD (stage IV dyspnea) [Ribeiro-Paes JT et al. Int J Chron Obstruct Pulmon Dis 2011]. All patients were treated with granulocyte colony-stimulating factor for 3 days immediately prior to bone marrow harvest. Autologous bone marrow mononuclear cells were isolated and infused into a peripheral vein. After 30 days, all patients showed a modest improvement in lung function, as measured by forced expiratory volume in 1 second (FEV₁). After 12 months, patients showed a significant improvement in quality of life and stable disease, suggesting a beneficial change in the natural history of COPD progression.

In summary, COPD is a heterogeneous disease, with major differences in risk factors, clinical features, and prognosis in different patient groups. Research in personalized medicine for COPD promises to provide effective treatment strategies that are tailored to the individual characteristics of each patient's disease. Genetic analysis, biomarker testing, and targeted therapy may soon be incorporated into the routine management of COPD.

• © 2011 MD Conference Express