Chest
Volume 144, Issue 5, November 2013, Pages 1659-1670
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Original Research
Genetic and Developmental Disorders
Systematic Review of Blood Biomarkers in Cystic Fibrosis Pulmonary Exacerbations

https://doi.org/10.1378/chest.13-0693Get rights and content

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.

Section snippets

Study Population

Our population of interest was defined as patients of all ages who were given a diagnosis of CF based on sweat chloride testing and/or CF transmembrane conductance regulator genotyping. Studies examining circulating (blood-based) biomarkers in patients with CF in the setting of CFPE were chosen for inclusion in this study. These biomarkers were evaluated according to their ability to aid in the diagnosis of CFPE, predict CFPE outcomes, and monitor response to CFPE treatment (Table 1). Studies

Study Selection

Our search strategy identified 5,596 potentially relevant abstracts and articles. Fifty studies were included in this review, and the process of study inclusion and exclusion is illustrated in Figure 1.

Study and Patient Characteristics

The characteristics of the included studies are detailed in Table 3. Most studies were conducted in the United Kingdom (46%), and the sample sizes were small, with just 10% of the studies involving > 50 participants with blood biomarker measurement.

The characteristics of patients included in the

Discussion

Current CFPE management is suboptimal because about one-quarter of patients fail to recover their previous baseline lung function despite therapy.7 Biomarkers of disease activity have the potential to aid in diagnosing CFPE earlier, predicting CFPE outcomes, and monitoring response to CFPE treatment. In this systematic review, we examined the use of blood-based biomarkers for each of these clinically relevant applications.

An ideal biomarker for use in CF should possess several characteristics.

Conclusions

In conclusion, to assist in knowledge dissemination and translation, we conducted an exhaustive review of the literature to identify promising blood-based biomarkers for clinical application in CFPEs. Although we identified several potential candidate blood biomarkers of disease activity, we also highlighted many of the research challenges that must be overcome prior to bringing these candidate biomarkers into clinical practice. Future studies of blood biomarkers will need to be larger with

Acknowledgments

Author contributions: Dr Quon had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Mr Shoki: contributed to the study design, literature search, and data extraction; data analysis and interpretation; and drafting and review of the manuscript for important intellectual content.

Dr Mayer-Hamblett: contributed to the data analysis and interpretation and drafting and review of the manuscript for important intellectual content.

Dr Wilcox:

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    Funding/Support: Dr Quon was supported by a Canadian Institute of Health Research (CIHR) Fellowship Award funded by the University of British Columbia and the Government of Canada.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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