@article{Molyneaux:2022:10.1164/rccm.202107-1769OC,
author = {Molyneaux, PL and Fahy, WA and Byrne, AJ and Braybrooke, R and Saunders, P and Toshner, R and Albers, G and Chua, F and Renzoni, EA and Wells, AU and Karkera, Y and Oballa, E and Saini, G and Nicholson, AG and Jenkins, G and Maher, TM},
doi = {10.1164/rccm.202107-1769OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1440--1448},
title = {CYFRA 21-1 predicts progression in IPF: a prospective longitudinal analysis of the PROFILE cohort},
url = {http://dx.doi.org/10.1164/rccm.202107-1769OC},
volume = {205},
year = {2022}
}

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TY  - JOUR
AB  - OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are a lack of effective biomarkers to guide therapeutic decision making. RATIONALE: To determine the relationship between serum levels of the cytokeratin fragment CYFRA 21-1 and disease progression and mortality in individuals with IPF enrolled in the PROFILE study. METHODS: CYFRA 21-1 was identified by immunohistochemistry in samples of human lung. Concentrations of CYFRA 21-1 were measured using an Elisa-based assay in serum, collected at baseline, 1- and 3-months, from 491 individuals with an incident diagnosis of IPF enrolled in the PROFILE study and from 100 control subjects. Study subjects were followed for a minimum of 3 years. MEASUREMENTS AND MAIN RESULTS: CYFRA 21-1 localises to hyperplastic epithelium in IPF lung. CYFRA 21-1 levels were significantly higher in IPF subjects compared to healthy controls in both discovery (n=132) (control 0.96±0.81 ng/mL versus IPF; 2.34±2.15 ng/mL, p < 0.0001) and validation (n=359) (control; 2.21±1.54 ng/mL and IPF; 4.13±2.77 ng/mL, p<0.0001) cohorts. Baseline levels of CYFRA 21-1 distinguished individuals at risk of 12-month disease progression (C-statistic 0.70 (95% CI 0.61-0.79), p < 0.0001) and were predictive of overall-mortality (HR 1.12 (1.06-1.19) per 1 ng/mL increase in CYFRA 21-1, p=0.0001). Furthermore, 3-month change in levels of CYFRA 21-1 separately predicted 12-month and overall survival in both the discovery and validation cohorts. CONCLUSIONS: CYFRA 21-1, a marker of epithelial damage and turnover, has the potential to be an important prognostic and therapeutic biomarker in individuals with IPF.
AU  - Molyneaux,PL
AU  - Fahy,WA
AU  - Byrne,AJ
AU  - Braybrooke,R
AU  - Saunders,P
AU  - Toshner,R
AU  - Albers,G
AU  - Chua,F
AU  - Renzoni,EA
AU  - Wells,AU
AU  - Karkera,Y
AU  - Oballa,E
AU  - Saini,G
AU  - Nicholson,AG
AU  - Jenkins,G
AU  - Maher,TM
DO  - 10.1164/rccm.202107-1769OC
EP  - 1448
PY  - 2022///
SN  - 1073-449X
SP  - 1440
TI  - CYFRA 21-1 predicts progression in IPF: a prospective longitudinal analysis of the PROFILE cohort
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.202107-1769OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35363592
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202107-1769OC
UR  - http://hdl.handle.net/10044/1/96287
VL  - 205
ER  - 

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