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Respir Res. 2019 Aug 5;20(1):176. doi: 10.1186/s12931-019-1147-2.

Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial.

Author information

1
The University of British Columbia Centre for Heart Lung Innovation (HLI), St Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
2
Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
3
Prevention of Organ Failure (PROOF) Centre of Excellence, 10th floor, 1190 Hornby Street, Vancouver, BC, V6Z 2K5, Canada.
4
Respiratory Division, Department of Medicine, Gordon and Leslie Diamond Health Care Centre, University of British Columbia, 7th Floor, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
5
Department of Computer Science, University of British Columbia, ICICS/CS Building 201-2366 Main Mall, Vancouver, BC, V6T 1Z4, Canada.
6
The University of British Columbia Centre for Heart Lung Innovation (HLI), St Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada. don.sin@hli.ubc.ca.
7
Respiratory Division, Department of Medicine, Gordon and Leslie Diamond Health Care Centre, University of British Columbia, 7th Floor, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada. don.sin@hli.ubc.ca.

Abstract

BACKGROUND:

Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD).

METHODS:

Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.1 ST microarray chips from two cohorts: 1) a prednisone cohort with 37 stable COPD patients randomly assigned to prednisone 30 mg/d + standard therapy for 4 days or standard therapy alone and 2) the Rapid Transition Program (RTP) cohort with 218 COPD patients who experienced AECOPD and were treated with systemic corticosteroids. All gene expression data were adjusted for the total number of white blood cells and their differential cell counts.

RESULTS:

In the prednisone cohort, 51 genes were differentially expressed between prednisone and standard therapy group at a false discovery rate of < 0.05. The top 3 genes with the largest fold-changes were KLRF1, GZMH and ADGRG1; and 21 genes were significantly enriched in immune system pathways including the natural killer cell mediated cytotoxicity. In the RTP cohort, 27 patients (12.4%) died within 1 year after hospitalisation of AECOPD; 32 of 51 genes differentially expressed in the prednisone cohort significantly changed from AECOPD to the convalescent state and were enriched in similar cellular immune pathways to that in the prednisone cohort. Of these, 10 genes including CX3CR1, KLRD1, S1PR5 and PRF1 were significantly associated with 1-year mortality.

CONCLUSIONS:

Short-term daily prednisone therapy produces a distinct blood gene signature that may be used to determine and monitor treatment responses to prednisone in COPD patients during AECOPD.

TRIAL REGISTRATION:

The prednisone cohort was registered at clinicalTrials.gov ( NCT02534402 ) and the RTP cohort was registered at ClinicalTrials.gov ( NCT02050022 ).

KEYWORDS:

Acute exacerbation; Blood; Chronic obstructive pulmonary disease; Gene expression; Microarray; Mortality; Prednisone

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