Predicting treatable traits for long-acting bronchodilators in patients with stable COPD

Abstract

Purpose

There is currently no measure to predict a treatability of long-acting β-2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) in patients with chronic obstructive pulmonary disease (COPD). We aimed to build prediction models for the treatment response to these bronchodilators, in order to determine the most responsive medication for patients with COPD.

Methods

We performed a prospective open-label crossover study, in which each long-acting bronchodilator was given in a random order to 65 patients with stable COPD for 4 weeks, with a 4-week washout period in between. We analyzed 14 baseline clinical traits, expression profiles of 31,426 gene transcripts, and damaged-gene scores of 6,464 genes acquired from leukocytes. The gene expression profiles were measured by RNA microarray and the damaged-gene scores were obtained after DNA exome sequencing. Linear regression analyses were performed to build prediction models after using factor and correlation analyses.

Results

Using a prediction model for a LABA, traits found associated with the treatment response were post-bronchodilator forced expiratory volume in 1 second, bronchodilator reversibility (BDR) to salbutamol, expression of three genes ( CLN8, PCSK5, and SKP2), and damage scores of four genes ( EPG5, FNBP4, SCN10A, and SPTBN5) ( R ²=0.512, p<0.001). Traits associated with the treatment response to a LAMA were COPD assessment test score, BDR, expression of four genes ( C1orf115, KIAA1618, PRKX, and RHOQ) and damage scores of three genes ( FBN3, FDFT1, and ZBED6) ( R ²=0.575, p<0.001). The prediction models consisting only of clinical traits appeared too weak to predict the treatment response, with R ²=0.231 for the LABA model and R ²=0.121 for the LAMA model.

Conclusion

Adding the expressions of genes and damaged-gene scores to the clinical traits may improve the predictability of treatment response to long-acting bronchodilators.

Journal

Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis

Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis

Journal ID (publisher-id): International Journal of COPD

Title: International Journal of Chronic Obstructive Pulmonary Disease

Publisher: Dove Medical Press

ISSN (Print): 1176-9106

ISSN (Electronic): 1178-2005

Publication date Collection: 2017

Publication date (Electronic): 12 December 2017

Volume: 12

Pages: 3557-3565

Affiliations

[1 ]Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul

[2 ]Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul

[3 ]Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam

[4 ]Division of Pulmonology, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri

[5 ]Department of Internal Medicine, Konkuk University Hospital, Konkuk University School of Medicine, Seoul

[6 ]Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea

Author notes

Correspondence: Yeon-Mok Oh, Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea, Tel [phone], Fax [phone], Email yeonmok.oh@ 123456gmail.com

Ju Han Kim, Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 03082, South Korea, Tel [phone], Fax [phone], Email juhan@ 123456snu.ac.kr

[*]

These authors contributed equally to this work

Article

Publisher ID: copd-12-3557

DOI: 10.2147/COPD.S151909

PMC ID: 5732547

Copyright statement: © 2017 Kang et al. This work is published and licensed by Dove Medical Press Limited

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Categories

Subject: Original Research