No 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 a 1 -antitrypsin (a1AT) levels at exacerbation onset were associated with an increased risk of being a nonresponder (i.e., failing to recover to baseline FEV 1 ). Baseline IL-8, neutrophil elastase antiprotease complexes, and a1AT along with changes in several plasma proteins with antibiotic treatment, in combination with FEV 1 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.

Background: Computer analysis of high-resolution CT (HRCT) scans may improve the assessment of structural lung injury in children with cystic fi brosis (CF). The goal of this cross-sectional pilot study was to validate automated, observer-independent image analysis software to establish objective, simple criteria for bronchiectasis and air trapping.