The profile study: A prospective study of fibrosis in lung endpoints to discover and qualify biomarkers for use in clinical trials

RATIONALE: Idiopathic Pulmonary Fibrosis(IPF) is an inexorably progressive condition of unknown aetiology with a median survival of less than 3 years. Current clinical tools only permit limited assessment of prognosis at diagnosis and fail to identify individuals with progressive disease. Biomarkers of disease progression and treatment responsiveness would be of use clinically and would greatly facilitate clinical trial design in IPF. We are prospectively evaluating a panel of serum proteins in individuals with well phenotyped IPF to assess their baseline and longitudinal value as disease biomarkers. METHODS: PRospective study Of Fibrosis In Lung Endpoints (PROFILE) is a multicentre, prospective cohort study of incident cases of IPF or Idiopathic Non-Specific Interstitial Pneumonia (NSIP), diagnosed by MDT assessment according to current criteria, from either secondary care centres (PROFILE Central England) or a specialist tertiary centre (PROFILE Brompton). Serum samples, together with relevant clinical investigations, are being collected from all subjects at 0, 1, 3 and 6months and at fixed time points thereafter. Concentrations of 109 serum protein biomarkers were analysed at Rules Based Medicine (Austin, Tx) using Luminex technology. Control, healthy volunteer, levels for each protein have been provided by Rules Based Medicine. RESULTS: Since September 2010, 158 subjects have been recruited (Brompton n=72, Central England n=86). Median age is 68 years and 78% are males. The two cohorts are well matched for age and gender. There is a trend to more severe disease at enrolment in the Brompton cohort. Serum proteins have thus far been measured in 155 samples (Baseline n=87, 1 month=52, 3 months n=29 and 6 months n=6). Approximately 32% of the serum proteins showed elevated levels in more than 50% of the subjects analysed. Two proteins, EGFR and Clusterin, were significantly lower in the serum of IPF subjects than healthy controls. In this initial analysis 35 analytes discern the IPF subjects from controls, including MMP1, MMP7, MMP9, PAI-1, SP-D, EGF and HGF. CONCLUSIONS: Individuals with IPF demonstrate marked alterations in a range of serum proteins. Initial analysis of our prospective cohort supports previous observations that MMP-1, MMP-7 and SP-D are elevated in IPF, and importantly, that these elevations can be reproducibly demonstrated at different time points. Further studies in this cohort will explore the utility of this panel of biomarkers in predicting patients at highest risk of subsequent disease progression.