Alborz Hakimi Shoki1, Nicole Mayer-Hamblett2, Pearce G Wilcox3, Don D Sin3, Bradley S Quon4. 1. University of Sydney Medical School, the University of Sydney, Sydney, NSW, Australia. 2. Department of Pediatrics, University of Washington, Seattle, WA. 3. James Hogg Research Centre, St. Paul's Hospital, Vancouver, BC, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 4. James Hogg Research Centre, St. Paul's Hospital, Vancouver, BC, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: bradley.quon@hli.ubc.ca.
Abstract
BACKGROUND: Biomarkers reflective of disease activity in cystic fibrosis (CF) have the potential to improve patient care, particularly during CF pulmonary exacerbations (CFPEs). Although blood-based biomarkers have been studied in CFPE for nearly 3 decades, none have been integrated into routine clinical practice. To facilitate progress in this area, we performed a systematic review evaluating blood-based biomarkers during CFPE. METHODS: MEDLINE, EMBASE, and CENTRAL were searched to identify relevant studies published from January 1995 to August 2012. We included all full-text studies examining systemic (blood-based) biomarkers to aid in the diagnosis of CFPE, predict outcomes of CFPE, and/or monitor the response to CFPE treatment. RESULTS: Seventy-eight unique blood-based biomarkers have been studied to date, mainly inflammatory cytokines, acute phase reactants, and markers of oxidative stress. C-reactive protein (CRP) consistently correlated with disease activity, with a statistically significant increase from stable to exacerbation state in five of six studies, and changes in response to CFPE treatment, with a statistically significant decrease from the beginning to the end of CFPE treatment in 18 of 20 studies. Other promising biomarkers of CFPE disease activity include neutrophil elastase antiproteinase complex, IL-6, myeloperoxidase (MPO), lactoferrin, and calprotectin. CONCLUSIONS: Although there are several blood-based biomarkers with evidence for application within the CFPE setting, CRP has been the most widely studied biomarker demonstrating the potential for clinical usefulness. Further validation studies and clinical trials are required to determine whether blood-based biomarkers can be used to ultimately improve health outcomes in the setting of a CFPE.
BACKGROUND: Biomarkers reflective of disease activity in cystic fibrosis (CF) have the potential to improve patient care, particularly during CF pulmonary exacerbations (CFPEs). Although blood-based biomarkers have been studied in CFPE for nearly 3 decades, none have been integrated into routine clinical practice. To facilitate progress in this area, we performed a systematic review evaluating blood-based biomarkers during CFPE. METHODS: MEDLINE, EMBASE, and CENTRAL were searched to identify relevant studies published from January 1995 to August 2012. We included all full-text studies examining systemic (blood-based) biomarkers to aid in the diagnosis of CFPE, predict outcomes of CFPE, and/or monitor the response to CFPE treatment. RESULTS: Seventy-eight unique blood-based biomarkers have been studied to date, mainly inflammatory cytokines, acute phase reactants, and markers of oxidative stress. C-reactive protein (CRP) consistently correlated with disease activity, with a statistically significant increase from stable to exacerbation state in five of six studies, and changes in response to CFPE treatment, with a statistically significant decrease from the beginning to the end of CFPE treatment in 18 of 20 studies. Other promising biomarkers of CFPE disease activity include neutrophil elastase antiproteinase complex, IL-6, myeloperoxidase (MPO), lactoferrin, and calprotectin. CONCLUSIONS: Although there are several blood-based biomarkers with evidence for application within the CFPE setting, CRP has been the most widely studied biomarker demonstrating the potential for clinical usefulness. Further validation studies and clinical trials are required to determine whether blood-based biomarkers can be used to ultimately improve health outcomes in the setting of a CFPE.
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