Inflammation biomarkers in sputum for clinical trials in cystic fibrosis: current understanding and gaps in knowledge.

Sputum biomarkers hold promise as a direct measure of inflammation within the cystic fibrosis (CF) lung, but variability in study design and sampling methodology have limited their use. A full evaluation of the reliability, validity and clinical relevance of individual biomarkers is required to optimise their use within CF clinical research. A biomarker Special Interest Working Group was established within the European Cystic Fibrosis Society-Clinical Trials Network Standardisation Committee, to perform a review of the evidence regarding sputum biomarkers in CF. From the 139 included articles, we identified 71 sputum biomarkers to undergo evaluation of their clinimetric properties, responsiveness, discriminant, concurrent and convergent validity. Current evidence confirms the potential of sputum biomarkers as outcome measures in clinical trials. Inconsistency in responsiveness, concurrent and convergent validity require further research into these markers and processing standardisation before translation into wider use. Of the 71 biomarkers identified, Neutrophil Elastase (NE), IL-8, TNF-α and IL-1β, demonstrated validity and responsiveness to be currently considered for use in clinical trials. Other biomarkers show future promise, including IL-6, calprotectin, HMGB-1 and YKL-40. A concerted international effort across the cystic fibrosis community is needed to promote high quality biomarker trial design, establish large population-based biomarker studies, and work together to create standards for collection, storage and analysis of sputum biomarkers