Effect of rehabilitation on biologic and transcriptomic responses after hospital-acquired deconditioning: a prospective longitudinal feasibility study

Abstract

Purpose

The objective of this study is to explore the transcriptomic and biologic variables characterizing the longitudinal rehabilitation intervention of patients with hospital-acquired deconditioning (HAD).

Methods

This prospective clinical trial recruited HAD patients (n = 10) who spent ≥3 weeks hospitalized and then received inpatient rehabilitation. Functional improvement was measured using the Functional Independence Measure (FIM). Transcriptomic and biological variables were recorded at rehabilitation admission and 1, 2, 4, and 6 weeks post-admission. RNA sequencing studied the temporal changes of gene expression in leukocytes. Between-subject transcriptome comparisons were performed using principle component analysis. Within-subject changes in gene expression were analyzed using a gene ontology hierarchical clustering to identify common biological terms. Heart rate, weight, albumin, creatinine, and complete blood counts were analyzed.

Results

Patients average age was 50.6 ± 7.2, FIM increased during inpatient rehabilitation (p = 0.01), weight increased (p = 0.01), lymphocytes decreased (p = 0.05), neutrophil increased (0.03) and red cell distribution width decreased (p = 0.05). The temporal profiles of gene expression revealed within-patient homogeneity and between-patients heterogeneity. The biological terms “bone morphogenesis” and “muscle cell development” were the most significantly enriched differentially expressed genes.

Conclusion

Transcriptomic and biologic markers paralleled the functional improvements of HAD patients during inpatient rehabilitation. Transcriptomic analyses were consistent with the cohort heterogeneity. Enrichment of the biological pathways bone morphogenesis and muscle cell development constituted evidence at the gene expression level of the effect of rehabilitation. Larger studies of various rehabilitation patient groups may increase gene expression profile homogeneity. Objective transcriptomic and biologic markers have the potential to improve the rehabilitation of HAD patients.

IMPLICATIONS FOR REHABILITATION

• Novel gene expression methods are increasingly being integrated into clinical practice and may apply to rehabilitation.

• Patients with hospital-acquired deconditioning (HAD) enriched gene expression of pathways targeted by inpatient rehabilitation such as bone morphogenesis and muscle cell development.

• The gene expression paralleled functional improvement of HAD patients.

• These data demonstrated the feasibility of molecular methods to identify markers of rehabilitation success in HAD patients.

Keywords:

• Hospital-acquired deconditioning
• inpatient rehabilitation
• biomarkers
• transcriptome
• bone morphogenesis

Acknowledgements

The authors thank the participants to this study and acknowledge The Ottawa Hospital Rehabilitation Centre staff for their assistance. The authors thank Ms. T. Backlund, Dr. T. Ramsay and Dr. R. Rodriguez for their assistance and Dr H. Uhthoff for his critical review of the manuscript.

Disclosure statement

The authors have no conflicts of interest to declare. Results of the investigation were presented, in part, at the 67th annual Canadian Association of Physical Medicine & Rehabilitation in 2019.

Additional information

Funding

This work was supported by the Academic Health Sciences Centre Alternate Funding Plan Innovation Fund, The Ottawa Hospital Academic Medical Organization [TOH-15-003].