Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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

Fingerprint

Cystic Fibrosis
Inflammation
Blood Proteins
Anti-Bacterial Agents
Serum Amyloid A Protein
Leukocyte Elastase
Therapeutics
Protease Inhibitors
Interleukin-8
C-Reactive Protein
Lung
Leukocyte L1 Antigen Complex
Interleukin 1 Receptor Antagonist Protein
Haptoglobins
Drug Discovery
Interleukin-1
Multicenter Studies
Interleukin-6
Proteins
Biomarkers

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation. / Sagel, Scott D.; Thompson, Valeria; Chmiel, James F.; Montgomery, Gregory; Nasr, Samya Z.; Perkett, Elizabeth; Saavedra, Milene T.; Slovis, Bonnie; Anthony, Margaret M.; Emmett, Peggy; Heltshe, Sonya L.

In: Annals of the American Thoracic Society, Vol. 12, No. 5, 01.05.2015, p. 708-717.

Research output: Contribution to journalArticle

Sagel, SD, Thompson, V, Chmiel, JF, Montgomery, G, Nasr, SZ, Perkett, E, Saavedra, MT, Slovis, B, Anthony, MM, Emmett, P & Heltshe, SL 2015, 'Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation', Annals of the American Thoracic Society, vol. 12, no. 5, pp. 708-717. https://doi.org/10.1513/AnnalsATS.201410-493OC
Sagel, Scott D. ; Thompson, Valeria ; Chmiel, James F. ; Montgomery, Gregory ; Nasr, Samya Z. ; Perkett, Elizabeth ; Saavedra, Milene T. ; Slovis, Bonnie ; Anthony, Margaret M. ; Emmett, Peggy ; Heltshe, Sonya L. / Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation. In: Annals of the American Thoracic Society. 2015 ; Vol. 12, No. 5. pp. 708-717.
@article{1ce5fdbfd0d14e3fb3877ba7c8af627d,
title = "Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation",
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",
author = "Sagel, {Scott D.} and Valeria Thompson and Chmiel, {James F.} and Gregory Montgomery and Nasr, {Samya Z.} and Elizabeth Perkett and Saavedra, {Milene T.} and Bonnie Slovis and Anthony, {Margaret M.} and Peggy Emmett and Heltshe, {Sonya L.}",
year = "2015",
month = "5",
day = "1",
doi = "10.1513/AnnalsATS.201410-493OC",
language = "English",
volume = "12",
pages = "708--717",
journal = "Annals of the American Thoracic Society",
issn = "2325-6621",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation

AU - Sagel, Scott D.

AU - Thompson, Valeria

AU - Chmiel, James F.

AU - Montgomery, Gregory

AU - Nasr, Samya Z.

AU - Perkett, Elizabeth

AU - Saavedra, Milene T.

AU - Slovis, Bonnie

AU - Anthony, Margaret M.

AU - Emmett, Peggy

AU - Heltshe, Sonya L.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Biomarker

KW - Cystic fibrosis

KW - Inflammation

KW - Plasma

KW - Pulmonary exacerbation

UR - http://www.scopus.com/inward/record.url?scp=84929611597&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929611597&partnerID=8YFLogxK

U2 - 10.1513/AnnalsATS.201410-493OC

DO - 10.1513/AnnalsATS.201410-493OC

M3 - Article

VL - 12

SP - 708

EP - 717

JO - Annals of the American Thoracic Society

JF - Annals of the American Thoracic Society

SN - 2325-6621

IS - 5

ER -