Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation

Scott D. Sagel, Valeria Thompson, James F. Chmiel, Gregory S. Montgomery, Samya Z. Nasr, Elizabeth Perkett, Milene T. Saavedra, Bonnie Slovis, Margaret M. Anthony, Peggy Emmett, Sonya L. Heltshe

Research output: Contribution to journalArticle

29 Scopus citations

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 α<inf>1</inf>-antitrypsin (α1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV<inf>1</inf>). Baseline IL-8, neutrophil elastase antiprotease complexes, and α1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV<inf>1</inf> 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.

Original languageEnglish (US)
Pages (from-to)708-717
Number of pages10
JournalAnnals of the American Thoracic Society
Volume12
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Biomarker
  • Cystic fibrosis
  • Inflammation
  • Plasma
  • Pulmonary exacerbation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Sagel, S. D., Thompson, V., Chmiel, J. F., Montgomery, G. S., Nasr, S. Z., Perkett, E., Saavedra, M. T., Slovis, B., Anthony, M. M., Emmett, P., & Heltshe, S. L. (2015). Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation. Annals of the American Thoracic Society, 12(5), 708-717. https://doi.org/10.1513/AnnalsATS.201410-493OC