Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation.
Ann Am Thorac Soc
; 12(5): 708-17, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25714657
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 MAINRESULTS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fibrose Cística
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Inflamação
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Pulmão
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Antibacterianos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article