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Ann Am Thorac Soc. 2015 May;12(5):708-17. doi: 10.1513/AnnalsATS.201410-493OC.

Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation.

Author information

1
1 Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado.

Abstract

RATIONALE:

In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation.

OBJECTIVES:

Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement.

METHODS:

In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older.

MEASUREMENTS AND MAIN RESULTS:

Significant reductions in 10 plasma proteins were observed in 103 patients who had paired blood collections during antibiotic treatment for pulmonary exacerbations. Plasma C-reactive protein, serum amyloid A, calprotectin, and neutrophil elastase antiprotease complexes correlated most strongly with clinical measures at exacerbation onset. Reductions in C-reactive protein, serum amyloid A, IL-1ra, and haptoglobin were most associated with improvements in lung function with antibiotic therapy. Having higher IL-6, IL-8, and α1-antitrypsin (α1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV1). Baseline IL-8, neutrophil elastase antiprotease complexes, and α1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV1 at exacerbation onset, were predictive of being a treatment responder.

CONCLUSIONS:

Circulating inflammatory proteins demonstrate and predict a response to treatment of CF pulmonary exacerbations. A systemic biomarker panel could speed up drug discovery, leading to a quicker, more efficient drug development process for the CF community.

KEYWORDS:

biomarker; cystic fibrosis; inflammation; plasma; pulmonary exacerbation

PMID:
25714657
PMCID:
PMC4418340
DOI:
10.1513/AnnalsATS.201410-493OC
[Indexed for MEDLINE]
Free PMC Article

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