Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO Registry.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which diagnosis and management remain challenging. Defining the circulating proteome in IPF may identify targets for biomarker development. We sought to quantify the circulating proteome in IPF, determine differential protein expression between subjects with IPF and controls, and examine relationships between protein expression and markers of disease severity. METHODS: This study involved 300 patients with IPF from the IPF-PRO Registry and 100 participants without known lung disease. Plasma collected at enrolment was analysed using aptamer-based proteomics (1305 proteins). Linear regression was used to determine differential protein expression between participants with IPF and controls and associations between protein expression and disease severity measures (percent predicted values for forced vital capacity [FVC] and diffusion capacity of the lung for carbon monoxide [DLco]; composite physiologic index [CPI]). Multivariable models were fit to select proteins that best distinguished IPF from controls. RESULTS: Five hundred fifty one proteins had significantly different levels between IPF and controls, of which 47 showed a |log2(fold-change)| > 0.585 (i.e. > 1.5-fold difference). Among the proteins with the greatest difference in levels in patients with IPF versus controls were the glycoproteins thrombospondin 1 and von Willebrand factor and immune-related proteins C-C motif chemokine ligand 17 and bactericidal permeability-increasing protein. Multivariable classification modelling identified nine proteins that, when considered together, distinguished IPF versus control status with high accuracy (area under receiver operating curve = 0.99). Among participants with IPF, 14 proteins were significantly associated with FVC % predicted, 23 with DLco % predicted, 14 with CPI. Four proteins (roundabout homolog-2, spondin-1, polymeric immunoglobulin receptor, intercellular adhesion molecule 5) demonstrated the expected relationship across all three disease severity measures. When considered in pathways analyses, proteins associated with the presence or severity of IPF were enriched in pathways involved in platelet and haemostatic responses, vascular or platelet derived growth factor signalling, immune activation, and extracellular matrix organisation. CONCLUSIONS: Patients with IPF have a distinct circulating proteome and can be distinguished using a nine-protein profile. Several proteins strongly associate with disease severity. The proteins identified may represent biomarker candidates and implicate pathways for further investigation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01915511).

The effect of a supervised community-based exercise program on balance, balance confidence, and gait in individuals with lower limb amputation.

BACKGROUND: Many individuals with lower limb loss report concern with walking ability after completing structured traditional rehabilitation. OBJECTIVES: The purpose of this study was to explore the impact of a supervised community-based exercise program on balance, balance confidence, and gait in individuals with lower limb amputation. STUDY DESIGN: Repeated measures. METHODS: The supervised exercise program was offered biweekly for 6 weeks. The GAITRite System by CIR Systems, Inc., the Figure-of-8 Walk Test, and Activity-specific Balance Confidence Scale were used to measure clinical outcomes pre- and post-intervention. RESULTS: In total, 16 participants with lower limb amputation (mean age: 50.8 years) completed the study. A multivariate, repeated measures analysis of variance indicated a statistically significant effect of training across six clinical outcome measures ( F(6, 10) = 4.514, p = .018). Moderate effect sizes were found for the Figure-of-8 Walk Test ( η2 = .586), Activity-specific Balance Confidence Scale ( η2 = .504), and gait velocity at comfortable walking speed ( η2 = .574). The average increase in gait speed was clinically meaningful at .14 m/s. CONCLUSION: The supervised community-based exercise program implemented in this study was designed to address specific functional needs for individuals with lower limb loss. Each participant experienced clinically meaningful improvements in balance, balance confidence, and walking ability. Clinical relevance The provision of a supervised community-based exercise program, after traditional rehabilitation, provides opportunity to offer a continuum of care that may enhance prosthetic functional ability and active participation in the community for individuals with lower limb amputation.