| Title: | Genetics plays a limited role in predicting chronic obstructive pulmonary disease treatment response and exacerbation |
| Journal: | Respiratory Medicine |
| Published: | 10 Aug 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34428673/ |
| DOI: | https://doi.org/10.1016/j.rmed.2021.106573 |
| URL: | http://www.resmedjournal.com/article/S0954611121002791/pdf |
Publication 13799
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Combination treatments, targeting multiple disease processes, benefit subjects with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, predicting treatment response and exacerbation risk remain challenging.</p>
OBJECTIVE: To identify genetic associations with AECOPD risk and response to combination therapy (fluticasone furoate, umeclidinium bromide and vilanterol).</p>
METHODS: The genetic basis of AECOPD disease was investigated in 19,841 subjects from 23 clinical studies and 2 disease cohorts to identify exacerbation disease targets. AECOPD pharmacogenetic effects were examined in 8439 moderate to severe COPD patients with exacerbation rate, lung function and quality of life endpoints; results were followed up in an additional 2201 subjects.</p>
RESULTS: We did not identify significant associations in the AECOPD disease analysis. In the AECOPD pharmacogenetics analysis, rs56195836 (MAPK8) was significantly associated with moderate to severe exacerbation rate in subjects on fluticasone furoate with baseline blood eosinophils ≥150 cells/μl (P = 1.8 × 10-8). Post-hoc, one variant was associated with on-treatment moderate to severe exacerbation rate stratifying by exacerbation history. AZU1 rs1962343 was significantly associated in subjects with frequent moderate exacerbation history when treated with fluticasone furoate/vilanterol (P = 1.1 × 10-8). Neither of these signals was supported in independent follow-up.</p>
CONCLUSION: Common genetic variants do not play major roles in AECOPD disease nor predict response to triple therapy or its components in moderate to very severe COPD.</p>
16 Keywords
- Androstadienes
- Antimicrobial Cationic Peptides
- Benzyl Alcohols
- Blood Proteins
- Chlorobenzenes
- Disease Progression
- Drug Therapy, Combination
- Genetic Association Studies
- Genetic Variation
- Lung
- Mitogen-Activated Protein Kinase 8
- Patient Acuity
- Pulmonary Disease, Chronic Obstructive
- Quality of Life
- Quinuclidines
- Treatment Outcome
11 Authors
- Louise Hosking
- Astrid Yeo
- Joshua Hoffman
- Mathias Chiano
- Dana Fraser
- Soumitra Ghosh
- David A Lipson
- Neil Martin
- Lynn D Condreay
- Charles Cox
- Pamela St Jean
1 Application
| Application ID | Title |
|---|---|
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
Enabling scientific discoveries that improve human health