Journal Information
Vol. 56. Issue 7.
Pages 420-421 (July 2020)
Vol. 56. Issue 7.
Pages 420-421 (July 2020)
Editorial
Full text access
Personalized Medicine in Chronic Obstructive Pulmonary Disease: How Close Are We?
Medicina personalizada en la enfermedad pulmonar obstructiva crónica: ¿cómo de cerca estamos?
Visits
1006
José Manuel Díaz Lópeza, Beatriz Giran Gonzáleza, Bernardino Alcázar-Navarreteb,c,
Corresponding author
balcazar@telefonica.net

Corresponding author.
a Servicio de Neumología, Hospital Universitario Virgen de las Nieves, Granada, Spain
b AIG de Medicina, Hospital de Alta Resolución de Loja, Agencia Sanitaria Hospital de Poniente, Granada, Spain
c CIBERES, Instituto de Salud Carlos III, Madrid, Spain
This item has received
Article information
Full Text
Bibliography
Download PDF
Statistics
Full Text

One of the major challenges currently facing medicine in general, and respiratory medicine in particular, is precision medicine.1 This approach, in which each patient receives the most appropriate treatment (pharmacological or otherwise) according to their characteristics (biological, genetic, environmental), optimizing the benefit and minimizing side effects, has been confirmed as a key strategy that will undoubtedly shift our daily care pathways from evidence-based medicine to personalized medicine.2

Although precision medicine initially began to develop in the areas of medical oncology and hereditary diseases, data are beginning to emerge in the field of respiratory medicine that will bring us closer to this approach.3 Indeed, now, at the end of the second decade of this century, these data are already influencing how we manage chronic obstructive pulmonary disease (COPD).

The first step toward precision medicine is the discovery of biomarkers that help us select different groups of patients who have shared therapeutic responses or disease patterns. This process began in the early years of this century and led to the concept of clinical phenotypes4 and the development of clinical practice guidelines, such as GesEPOC, the Spanish COPD guidelines, that are based on clinical phenotypes.5 The clinical phenotype concept is merely an intermediate step and does not fully encompass the notion of precision medicine, so more progress in this area is necessary. This is the current situation with regard to the so-called “treatable traits”.6

The most studied treatable trait in recent years in the field of COPD is the presence of eosinophils in peripheral blood.7 Eosinophil concentrations in peripheral blood are a reliable biomarker of response to inhaled corticosteroids (ICS)8 in terms of reducing exacerbations compared to other therapeutic options. It is also a marker of the risk of side effects from ICS use (such as pneumonia). In fact, the number needed to treat (NNT) with ICS to prevent at least 1 moderate or severe exacerbation in the subgroup of patients with a high eosinophil count (>300cells/mL) is less than 10. However, eosinophils only appear to play a role in the prevention of exacerbations in patients with frequent exacerbations, and the role of this biomarker in non-exacerbators is less clear.9,10 Following the latest GOLD 2019 recommendations released at the end of last year, eosinophil counts are now one of the first examples of COPD precision medicine included in clinical practice guidelines.11

We also have examples of precision medicine in the field of bronchodilators. Perhaps one of the most interesting comes from a post hoc analysis of the POET-COPD study which investigated differences in response to 2 long-acting bronchodilators in the prevention of exacerbations.12 In this study, patients with the β2-adrenergic receptor (ADRB2) polymorphism Arg16Arg had a better response to salmeterol in the prevention of exacerbations compared to carriers of other polymorphisms (Arg16Gly and Gly16Gly).

More recently, a study of 64 COPD patients in an open-label crossover clinical trial13 demonstrated that different clinical characteristics, along with gene expression and damaged-gene scores, can help predict which patients will respond significantly to the use of bronchodilators (defining this response as an increase of >100mL in FEV1 after 4 weeks of pharmacological treatment).

Finally, data from a recent crossover clinical trial14 have shown that different pharmacological responses in COPD can be seen in different drug families, and even within the same drug family, individual response may vary considerably. In this clinical trial, which compared 2 marketed dual bronchodilator (DB) combinations, 52% of patients showed a clinically significant response in terms of FEV1 to one of the DBs and 19% of patients responded similarly to the other. This effect was observed in both the previously treated population and the treatment-naïve population.15 Unfortunately, no blood samples were obtained during this study that would help define which biomarkers indicated a higher probability of responding to one DB or the other.

In conclusion, we are beginning to see examples of precision medicine in the field of COPD, and the results achieved with this type of approach are more promising than with “one size fits all” medicine. However, we are still only halfway there, and we will need clinical trials in the coming years to assess the real effectiveness of interventions based on similar clinical and biological patterns. To this end, the search for biomarkers and the re-analysis of large databases that contain data on the different “omics” in COPD will be equally necessary.

Conflict of Interests

Dr. Díaz López declares no conflicts of interest associated with this article. Dr. Girán González declares no conflicts of interest associated with this article. Dr. Alcázar-Navarrete declares that he has received personal honoraria, grants for research projects and non-financial aid in the last 5 years from GSK, Novartis AG, Boehringer Ingelheim, Chiesi, Laboratorios Menarini, and Astra-Zeneca, unassociated with this article. Dr. Alcázar-Navarrete is also the holder of registered patent P201730724.

References
[1]
F.S. Collins, H. Varmus.
A new initiative on precision medicine.
N Engl J Med, 372 (2015), pp. 793-795
[2]
R. Hodson.
Precision medicine.
Nature, 537 (2016), pp. S49
[3]
B.W. Ramsey, J. Davies, N.G. McElvaney, E. Tullis, S.C. Bell, P. Dřevínek, et al.
A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
N Engl J Med, 365 (2011), pp. 1663-1672
[4]
G.R. Washko, G. Parraga.
COPD biomarkers and phenotypes: opportunities for better outcomes with precision imaging.
Eur Respir J, 52 (2018), pp. 1801570
[5]
M. Miravitlles, J.J. Soler-Cataluña, M. Calle, J. Molina, P. Almagro, J.A. Quintano, et al.
Spanish Guidelines for Management of Chronic Obstructive Pulmonary Disease (GesEPOC) 2017. Pharmacological treatment of stable phase.
Arch Bronconeumol, 53 (2017), pp. 324-335
[6]
A. Agusti, E. Bel, M. Thomas, C. Vogelmeier, G. Brusselle, S. Holgate, et al.
Treatable traits: toward precision medicine of chronic airway diseases.
Eur Respir J, 47 (2016), pp. 410-419
[7]
G. Brusselle, I.D. Pavord, S. Landis, S. Pascoe, S. Lettis, N. Morjaria, et al.
Blood eosinophil levels as a biomarker in COPD.
Respir Med, 138 (2018), pp. 21-31
[8]
S. Pascoe, N. Barnes, G. Brusselle, C. Compton, G.J. Criner, M.T. Dransfield, et al.
Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.
Lancet Respir Med, 7 (2019), pp. 745-756
[9]
J.H. Yun, A. Lamb, R. Chase, D. Singh, M.M. Parker, A. Saferali, et al.
Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease.
J Allergy Clin Immunol, 141 (2018), pp. 2037-2047.e10
[10]
D. Singh.
Predicting corticosteroid response in chronic obstructive pulmonary disease. Blood eosinophils gain momentum.
Am J Respir Crit Care Med, 196 (2017), pp. 1098-1100
[11]
D. Singh, A. Agusti, A. Anzueto, P.J. Barnes, J. Bourbeau, B.R. Celli, et al.
Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019.
Eur Respir J, 53 (2019), pp. 1900164
[12]
K.F. Rabe, L.M. Fabbri, E. Israel, H. Kögler, K. Riemann, H. Schmidt, et al.
Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial.
Lancet Respir Med, 2 (2014), pp. 44-53
[13]
J. Kang, K.T. Kim, J.S.J.-H. Lee, E.K. Kim, T.-H. Kim, K.H. Yoo, et al.
Predicting treatable traits for long-acting bronchodilators in patients with stable COPD.
Int J Chron Obstruct Pulmon Dis, 12 (2017), pp. 3557-3565
[14]
G.J. Feldman, A.R. Sousa, D.A. Lipson, L. Tombs, N. Barnes, J.H. Riley, et al.
Comparative efficacy of once-daily umeclidinium/vilanterol and tiotropium/olodaterol therapy in symptomatic chronic obstructive pulmonary disease: a randomized study.
Adv Ther, 34 (2017), pp. 2518-2533
[15]
B. Alcázar Navarrete, I. Boucot, I. Naya, L. Tombs, D.A. Lipson, C. Compton, et al.
Umeclidinium/vilanterol versus tiotropium/olodaterol in maintenance-naïve patients with moderate symptomatic chronic obstructive pulmonary disease: a post hoc analysis.
Pulm Ther, 4 (2018), pp. 171-183

Please cite this article as: Díaz López JM, Giran González B, Alcázar-Navarrete B. Medicina personalizada en la enfermedad pulmonar obstructiva crónica: ¿cómo de cerca estamos? Arch Bronconeumol. 2020;56:420–421.

Copyright © 2019. SEPAR
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?