Biology subjects

Braybrooke, R.

Publications and source records attributed to Braybrooke, R..

2 recordsLinked to original sources

bioRxiv2018

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was assessed in 145 newly-diagnosed individuals with IPF. Serum levels of collagen synthesis neoepitopes, PRO-C3 and PRO-C6 (collagen type 3 and 6), were elevated in IPF compared with controls at baseline, and progressive disease versus stable disease during follow up, (PRO-C3 p<0.001; PRO-C6 p=0.029). Assessment of rate of change in neoepitope levels from baseline to 3 months (defined as slope to month 3: HIGH slope, slope > 0 vs. LOW slope, slope <=0) demonstrated no relationship with mortality for these markers (PRO-C3 (HR 1.62, p=0.080); PINP (HR 0.76, p=0.309); PRO-C6 (HR 1.14, p=0.628)). As previously reported, rising concentrations of collagen degradation markers C1M, C3M, C6M and CRPM were associated with an increased risk of overall mortality (HR=1.84, CI 1.03 - 3.27, p=0.038, HR=2.44, CI 1.39-4.31, p=0.002; HR= 2.19, CI 1.25-3.82, p=0.006; HR= 2.13 CI 1.21-3.75, p=0.009 respectively). Elevated levels of PRO-C3 and PRO-C6 associate with IPF disease progression. Collagen synthesis and degradation biomarkers have the potential to enhance clinical trials in IPF and may inform prognostic assessment and therapeutic decision making in the clinic.

clinical trials↗

bioRxiv2018

Patient reported distress can aid clinical decision making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease. We aimed to determine if patient response to a palliative assessment survey could predict disease progression or death. We undertook a cross-sectional study in a UK clinical cohort of incident cases. Rasch-based methodology provided a disease distress value from an abridged 11 item model of the original 45 item survey. Distress values were compared with measures of lung function. Disease progression or mortality alone was predicted at twelve months from survey completion, with risk of death assessed at three, six and twelve months. Disease distress values were negatively correlated with lung function (r=-0.275 percent predicted DLCO). Expected survey scores computed from distress values could distinguish disease progression, 8.8 (p=0.004), and people who died, 10.2 (p=0.002), from those who did not progress, 6.9. Actual survey scores predicted disease progression and mortality with an area under the curve of 0.60 and 0.64, respectively. Each point increment in actual score increased risk of twelve-month mortality by 10%, almost 43% of people scoring above 18 did not survive beyond 105 days. We define a short questionnaire that can score disease distress and predict prognosis, assisting clinical decision making in progressive fibrosis.

clinical trials↗